The Genetic Approach to Controlling BSE
By: David A. Rodger
Stephen Moore was on holiday in his native
Australia back in May 2003, when he received
the telephone call that changed his life. "A Canadian
reporter was on the line asking me to
comment on a case of bovine spongiform encephalopathy
(BSE) in Alberta," says Dr.
Moore "I still don't know how he tracked me
down. There wasn't much I could say because,
of course, this was news to me."
Back in Edmonton, where he is Chair of Bovine
Genomics in the University of Alberta's
Department of Agricultural, Food and Nutritional
Science, Dr. Moore was quickly brought
up to date. He and his research group had
been intimately involved in mapping the bovine
genome and were considered leaders in identifying
and characterizing genes that affect cattle
growth, yield, fat content and meat tenderness.
"There's a genetic component in BSE susceptibility,"
he explains. "You only have to look at
the UK where some animals in a herd came
down with the disease while others didn't.
This was despite their having eaten the same
contaminated feed. What are the genetic factors
that render cattle more susceptible or
more resistant to BSE? The answers will help
us with intervention, diagnosis, and treatment."
In January 2006, the Alberta Prion Research
Institute appointed Dr. Moore its first scientific
director. Dr. Moore also leads PrioNet's Research
Theme I on BSE. He is Principal Investigator
on two APRI-PrioNet co-funded projects ...2
BSE
- one related to BSE and the other to Chronic Wasting
Disease. Other partners include the University of Alberta,
National Microbiology Laboratories - Public
Health Agency of Canada, National Centre for Foreign
Animal Disease - Canadian Food Inspection Agency.
"The only place in the world that has had a statistically
significant number of BSE cases is the UK," he says.
"The number in Canada is, thankfully, too few for genetic
analysis. So, two of my students went to the
Rosslyn Institute in Scotland to extract DNA from the
blood samples gathered from BSE-infected cattle. That
trip was necessary because blood samples are infectious
and can't be brought into Canada, while DNA
samples are harmless and can be imported. We're now
analyzing the DNA."
In late July 2006, another case of BSE was discovered,
involving a 50-month old Alberta dairy cow born long
after Canada's ban on the use of cattle parts in cattle
feed. How close is a test that detects BSE and other
TSEs in live healthy animals? When will we be able to
detect them in live animals as opposed to postmortem?
"Before there can be a valid test - dozens are in trials
now - two issues must be resolved," says Dr. Moore.
"First, it must be easy to collect a sample, and second,
it can't cost too much. If the test costs more than the
animal is worth, it's of little benefit to producers." For
more information visit the Alberta Prion Research
Institute web site at http://www.prioninstitute.ca. •
Coming to terms with Chronic Wasting disease
By: David A. Rodger
PrioNet's Scientific Director, Neil Cashman,
has referred to chronic wasting disease
(CWD) as "the threat in our own backyard."
Indeed, it could be the Transmissible
Spongiform Encephalopathy with the greatest
potential for species devastation. Leading
PrioNet's Theme 2 efforts to understand and
control CWD is Ted Leighton of the Western
College of Veterinary Medicine in Saskatoon.
Dr. Leighton is recognized internationally for
his research into wildlife diseases. So it will
surprise many to discover that he did his
undergraduate work at Cornell University not
in science but in Theatre Arts. "Theatre Arts
had liberal course requirements," he explains,
"enabling me to take natural science, social
science and humanities in a mix that provided
an excellent general education." He received
his veterinary degree from the University of
Saskatchewan in 1979, completed a Ph.D. in
veterinary pathology at Cornell in 1984, and
returned to the University of Saskatchewan
later that year as professor of veterinary
pathology.
Currently Dr. Leighton is Executive Director
of the Canadian Cooperative Wildlife Health
Centre, which is headquartered in Saskatoon.
The organization is a partnership among
Canada's veterinary colleges and government
agencies responsible for wildlife management,
agriculture, and public health. The Centre's
mandate is one of disease surveillance. It has
programs to monitor the occurrence and
spread of such diseases as avian influenza,
West Nile virus, and CWD (since 1997).
CWD on elk farms in Saskatchewan and
Alberta has been eradicated through a
systematic program of culling infected or
exposed animals. Unfortunately, CWD in wild
animals, especially white-tailed and mule deer,
is much harder to deal with. Two years ago,
the Centre brought together international
...2
CWD
experts in CWD, disease monitoring, deer biology, and other specialties to help determine
whether CWD in wild deer in Canada represented a potential crisis. They determined that it
does.
"They told us Canada had a few years to develop its response to CWD," he recalls, "because
this is a slow-moving disease. They recommended that Canada take determined action to
control the disease in wild deer, but warned that there were no proven methods of doing this
and that scientific research carried out in the affected areas would have to guide any effective
response. They emphasized that there would be large social, ecological or economic
consequences for Canada if we do not stop the spread of CWD in wild deer."
Dr. Leighton praises the foresight that led to PrioNet's creation, and the flexibility the network
has been given to deal with a disease that was, until recently, overshadowed by BSE concerns in
Canada. "Our priority with respect to CWD is to learn as much as we can about how it is
transmitted. Only then can we develop a program to contain and eliminate it." •
Coming Together
PrioNet established its Student and
Young Professional Association
(SYPA) at its recent Annual General
Meeting 2006. Joel Watts and Qasim
Khan (University of Toronto) are
SYPA's interim leaders.
SYPA includes graduate students,
post-doctoral fellows, research associates,
and research technicians who
are involved with PrioNet's network
investigators. The purpose of this
association is to organize studentfocused
events; liaise with PrioNet
regarding issues surrounding students
and young professionals; and work
together to capitalize on the different
programs PrioNet has available to
strengthen their research and training
experience.
PrioNet will be implementing a variety
of education and training programs to
facilitate learning exchange and enrich
the experience of students and young
professionals within the network. For
resources such as job postings and
training updates related to students
and young professionals, visit the Education
and Training link at
http://www.prionetcanada.ca. •
PrioNet's Research Projects Related to CWD & BSE
PrioNet Canada will address Canadian prion challenges through its five research themes. The
theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy
and Chronic Wasting Disease are outlined below:
Research Theme I: Bovine Spongiform Encephalopathy
Theme Leader: Dr. Steven Moore, University of Alberta
Associate Leader: Dr. Mike Belosevic, University of Alberta
Theme Pathologist: Dr. Stefanie Czub, Canadian Food Inspection Agency
A Comprehensive and Comparative Approach to Genetics & Pathobiology of Prion
Disease
Principal Investigator: Dr. Steven Moore, University of Alberta
Co-Investigators:
Dr. John Williams, Parco Tecnologico Padano, Italy
Dr. Michael Coulthart, Public Health Agency of Canada
Dr. Denny Crews, Agriculture & Agri-food Canada
Dr. Stefanie Czub, Canadian Food Inspection Agency
Dr. Michael Heaton, US Department of Agriculture
Prion Inactivation and Environment
Principal Investigator: Dr. Mike Belosevic, University of Alberta
Co-Investigators:
Dr. Norman Neumann, University of Calgary
Dr. Neil Cashman, University of British Columbia
Dr. Daniel Smith, University of Alberta
Dr. Steven Craik, University of Alberta
Dr. Mohamed Gamal El-Din, University of Alberta
Dr. Phillip Fedorak, University of Alberta
Immunoprophylaxis of Bovine Spongiform Encephalopathy
Principal Investigator: Dr. Andrew A. Potter, University of Saskatchewan
Co-Investigators:
Dr. Philip Griebel, University of Saskatchewan
Dr. Scott Napper, University of Saskatchewan
Dr. Lorne Babiuk, University of Saskatchewan
Research Theme II: Chronic Wasting Disease
Theme Leader: Dr. Ted Leighton, University of Saskatchewan
Associate Theme Leader: Dr. Cheryl Waldner, University of Saskatchewan
Sub-Theme Leader (for Scrapie): Dr. Aru Balachandran, Canadian Food Inspection Agency
Factors Affecting Prevalence and Geographic Spread of Chronic Wasting Disease in
Wild Deer in Saskatchewan (Phase I & II)
Principal Investigator: Dr. Trent Bollinger, University of Saskatchewan
Co-Investigators:
Dr. Dave Coltman, University of Alberta
Dr. Ted Leighton, Canadian Cooperative Wildlife Health Centre, University of Saskatchewan
Dr. Francois Messier, University of Saskatchewan
Dr. Cheryl Waldner, Western College of Veterinary Medicine, University of Saskatchewan
A Comparative Approach Examining Host Response to TSE Infection by Serial Analysis
of Gene Expression (microSAGE) in Cervids and Ovids
Principal Investigator: Dr. Stephen Moore, University of Alberta
Co-Investigators:
Dr. Michael Brownstein, J. Craig Venter Institute
Dr. Mike Miller, Wildlife Research Centre, Colorado
Dr. Catherine Graham, Canadian Food Inspection Agency
Dr. Aru Balachandran, Canadian Food Inspection Agency
PrioNet's Research Projects Related to CWD & BSE
PrioNet Canada will address Canadian prion challenges through its five research themes. The
theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy
and Chronic Wasting Disease are outlined below:
Stay tuned to upcoming
issues of PrioNews as
we feature PrioNet's
three other research
themes:
==================================END
DNA polymorphisms of the prion doppel gene region in four different German
cattle breeds and cows tested positive for bovine spongiform encephalopathy
Journal Mammalian Genome
Publisher Springer New York
ISSN 0938-8990 (Print) 1432-1777 (Online)
Subject Biomedical and Life Sciences and Medicine
Issue Volume 16, Number 11 / November, 2005
DOI 10.1007/s00335-005-0052-9
Pages 884-892
Online Date Saturday, November 12, 2005
N. Balbus1, A. Humeny1, K. Kashkevich1, I. Henz1, C. Fischer2, C.-M. Becker1
and K. Schiebel1
(1) Institut für Biochemie, Emil-Fischer-Zentrum, Universität
Erlangen-Nürnberg, Fahrstrasse 17, 91054 , Erlangen, Germany
(2) Institut für Humangenetik, Universität Heidelberg, Im Neuenheimer Feld
366, 69120, Heidelberg, Germany
Received: 5 April 2005 Accepted: 18 July 2005 Published online: 11
November 2005
Abstract Polymorphisms of the prion protein gene PRNP have been shown to
influence the susceptibility/resistance to prion infections in human and
sheep. In addition, the T174M polymorphism within the flanking prion doppel
gene (PRND) was thought to be involved in susceptibility to sporadic
Creutzfeldt-Jacob disease. To study a possible influence of DNA
polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy
(BSE), previously identified and newly isolated DNA polymorphisms were
genotyped in all available German cattle that tested positive for BSE.
Genotypes and calculated haplotypes were compared with breeding bulls
serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein
Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh
(Swiss Brown) resulted in the isolation of the previously known
polymorphisms R50H and R132Q and two novel synonymous single nucleotide
polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype
analysis of BSE and control animals revealed a significantly different
distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not
in the other breeds tested. No association to BSE susceptibility was
detectable for polymorphisms R50H and A5063T.
----------------------------------------------------------------------------
----
K. Schiebel
Email: [email protected]
Phone: 49-9131 85-26206
Fax: 49-9131 85-22485
References secured to subscribers.
http://www.springerlink.com/content/y12 ... abec8&pi=7
Subject: Atypical BSE in Germany-Proof of transmissibility and biochemical
characterization
Date: August 20, 2006 at 3:33 pm PST
Copyright © 2006 Elsevier B.V. All rights reserved.
Atypical BSE in Germany-Proof of transmissibility and biochemical
characterization
A. Buschmanna, A. Gretzschela, A.-G. Biacabeb, K. Schiebelc, C. Coronad, C.
Hoffmanna, M. Eidena, T. Baronb, C. Casaloned and Martin H. Groschupa, ,
aFriedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging
Infectious Diseases, Boddenblick 5a, 17493 Greifswald, Insel Riems, Germany
bAFSSA-Lyon, Unite ATNC, Lyon, France
cInstitut für Biochemie, Universitity Erlangen-Nürnberg, Germany
dCEA, Instituto Zooprofilattico di Turino, Turin, Italy
Received 11 January 2006; revised 23 May 2006; accepted 2 June 2006.
Available online 17 August 2006.
Abstract
Intensive active surveillance has uncovered two atypical German BSE cases in
older cattle which resemble the two different atypical BSE phenotypes that
have recently been described in France (designated H-type) and Italy
(designated L-type or BASE). The H-type is characterized by a significantly
higher molecular size, but a conventional glycopattern of the proteinase K
treated abnormal prion protein (PrPSc), while the L-type PrPSc has only a
slightly lower molecular size and a distinctly different glycopattern. In
this paper we describe the successful transmission of both German atypical
BSE cases to transgenic mice overexpressing bovine PrPC. Upon challenge with
the L-type, these mice developed BSE after a substantially shorter
incubation period than any classical BSE transmission using these mice to
date. In contrast, the incubation period was distinctly prolonged when these
mice were challenged with the H-type. PrPSc accumulated in the brains of
these mice were of the same atypical BSE type that had been used for the
transmission. These atypical cases suggest the possible existence of
sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in
the UK could have also been initiated by an intraspecies transmission from a
sporadic BSE case.
Keywords: BSE; Cattle; PrPSc; Biochemical differentiation
http://www.sciencedirect.com/
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 45, pp. 37408–37414, November 11, 2005
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A.
Bovine Prion Protein Gene (PRNP) Promoter Polymorphisms
Modulate PRNP Expression and May Be Responsible for
Differences in Bovine Spongiform Encephalopathy
Susceptibility*□S
Received for publication, June 10, 2005, and in revised form, July 20, 2005 Published, JBC Papers in Press, September 1, 2005, DOI 10.1074/jbc.M506361200
Petra Sander‡, Henning Hamann‡, Cord Dro¨gemu¨ ller‡, Kseniya Kashkevich§, Katrin Schiebel§, and Tosso Leeb‡1
From the ‡Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Bu¨nteweg 17p, 30559 Hannover, Germany
and the §Institute for Biochemistry, University of Erlangen-Nu¨rnberg, Fahrstrasse 17, 91054 Erlangen, Germany
The susceptibility of humans to the variant Creutzfeldt-Jakob
disease is greatly influenced by polymorphisms within the human
prion protein gene (PRNP). Similar genetic differences exist in
sheep, in which PRNP polymorphisms modify the susceptibility to
scrapie. However, the known coding polymorphisms within the
bovine PRNP gene have little or no effect on bovine spongiform
encephalopathy (BSE) susceptibility in cattle. We have recently
found a tentative association between PRNP promoter polymorphisms
and BSE susceptibility in German cattle (Sander, P.,
Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M.,
Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19–25).A
plausible hypothesis explaining this observation could be that the
bovine PRNP promoter polymorphisms cause changes in PRNP
expression that might be responsible for differences in BSE incubation
time and/or BSE susceptibility. To test this hypothesis, we performed
a functional promoter analysis of the different bovine PRNP
promoter alleles by reporter gene assays in vitro and by measuring
PRNPmRNAlevels in calves with different PRNP genotypes in vivo.
Twovariable sites, a 23-bp insertion/deletion (indel) polymorphism
containing a RP58-binding site and a 12-bp indel polymorphism
containing an SP1-binding site, were investigated. Band shift assays
indicated differences in transcription factor binding to the different
alleles at the two polymorphisms. Reporter gene assays demonstrated
an interaction between the two postulated transcription factors and
lower expression levels of the ins/ins allele compared with the del/del
allele. The in vivo data revealed substantial individual variation of
PRNP expression in different tissues. In intestinal lymph nodes,
expression levels differed between the different PRNP genotypes. ...SNIP...END...TSS
By: David A. Rodger
Stephen Moore was on holiday in his native
Australia back in May 2003, when he received
the telephone call that changed his life. "A Canadian
reporter was on the line asking me to
comment on a case of bovine spongiform encephalopathy
(BSE) in Alberta," says Dr.
Moore "I still don't know how he tracked me
down. There wasn't much I could say because,
of course, this was news to me."
Back in Edmonton, where he is Chair of Bovine
Genomics in the University of Alberta's
Department of Agricultural, Food and Nutritional
Science, Dr. Moore was quickly brought
up to date. He and his research group had
been intimately involved in mapping the bovine
genome and were considered leaders in identifying
and characterizing genes that affect cattle
growth, yield, fat content and meat tenderness.
"There's a genetic component in BSE susceptibility,"
he explains. "You only have to look at
the UK where some animals in a herd came
down with the disease while others didn't.
This was despite their having eaten the same
contaminated feed. What are the genetic factors
that render cattle more susceptible or
more resistant to BSE? The answers will help
us with intervention, diagnosis, and treatment."
In January 2006, the Alberta Prion Research
Institute appointed Dr. Moore its first scientific
director. Dr. Moore also leads PrioNet's Research
Theme I on BSE. He is Principal Investigator
on two APRI-PrioNet co-funded projects ...2
BSE
- one related to BSE and the other to Chronic Wasting
Disease. Other partners include the University of Alberta,
National Microbiology Laboratories - Public
Health Agency of Canada, National Centre for Foreign
Animal Disease - Canadian Food Inspection Agency.
"The only place in the world that has had a statistically
significant number of BSE cases is the UK," he says.
"The number in Canada is, thankfully, too few for genetic
analysis. So, two of my students went to the
Rosslyn Institute in Scotland to extract DNA from the
blood samples gathered from BSE-infected cattle. That
trip was necessary because blood samples are infectious
and can't be brought into Canada, while DNA
samples are harmless and can be imported. We're now
analyzing the DNA."
In late July 2006, another case of BSE was discovered,
involving a 50-month old Alberta dairy cow born long
after Canada's ban on the use of cattle parts in cattle
feed. How close is a test that detects BSE and other
TSEs in live healthy animals? When will we be able to
detect them in live animals as opposed to postmortem?
"Before there can be a valid test - dozens are in trials
now - two issues must be resolved," says Dr. Moore.
"First, it must be easy to collect a sample, and second,
it can't cost too much. If the test costs more than the
animal is worth, it's of little benefit to producers." For
more information visit the Alberta Prion Research
Institute web site at http://www.prioninstitute.ca. •
Coming to terms with Chronic Wasting disease
By: David A. Rodger
PrioNet's Scientific Director, Neil Cashman,
has referred to chronic wasting disease
(CWD) as "the threat in our own backyard."
Indeed, it could be the Transmissible
Spongiform Encephalopathy with the greatest
potential for species devastation. Leading
PrioNet's Theme 2 efforts to understand and
control CWD is Ted Leighton of the Western
College of Veterinary Medicine in Saskatoon.
Dr. Leighton is recognized internationally for
his research into wildlife diseases. So it will
surprise many to discover that he did his
undergraduate work at Cornell University not
in science but in Theatre Arts. "Theatre Arts
had liberal course requirements," he explains,
"enabling me to take natural science, social
science and humanities in a mix that provided
an excellent general education." He received
his veterinary degree from the University of
Saskatchewan in 1979, completed a Ph.D. in
veterinary pathology at Cornell in 1984, and
returned to the University of Saskatchewan
later that year as professor of veterinary
pathology.
Currently Dr. Leighton is Executive Director
of the Canadian Cooperative Wildlife Health
Centre, which is headquartered in Saskatoon.
The organization is a partnership among
Canada's veterinary colleges and government
agencies responsible for wildlife management,
agriculture, and public health. The Centre's
mandate is one of disease surveillance. It has
programs to monitor the occurrence and
spread of such diseases as avian influenza,
West Nile virus, and CWD (since 1997).
CWD on elk farms in Saskatchewan and
Alberta has been eradicated through a
systematic program of culling infected or
exposed animals. Unfortunately, CWD in wild
animals, especially white-tailed and mule deer,
is much harder to deal with. Two years ago,
the Centre brought together international
...2
CWD
experts in CWD, disease monitoring, deer biology, and other specialties to help determine
whether CWD in wild deer in Canada represented a potential crisis. They determined that it
does.
"They told us Canada had a few years to develop its response to CWD," he recalls, "because
this is a slow-moving disease. They recommended that Canada take determined action to
control the disease in wild deer, but warned that there were no proven methods of doing this
and that scientific research carried out in the affected areas would have to guide any effective
response. They emphasized that there would be large social, ecological or economic
consequences for Canada if we do not stop the spread of CWD in wild deer."
Dr. Leighton praises the foresight that led to PrioNet's creation, and the flexibility the network
has been given to deal with a disease that was, until recently, overshadowed by BSE concerns in
Canada. "Our priority with respect to CWD is to learn as much as we can about how it is
transmitted. Only then can we develop a program to contain and eliminate it." •
Coming Together
PrioNet established its Student and
Young Professional Association
(SYPA) at its recent Annual General
Meeting 2006. Joel Watts and Qasim
Khan (University of Toronto) are
SYPA's interim leaders.
SYPA includes graduate students,
post-doctoral fellows, research associates,
and research technicians who
are involved with PrioNet's network
investigators. The purpose of this
association is to organize studentfocused
events; liaise with PrioNet
regarding issues surrounding students
and young professionals; and work
together to capitalize on the different
programs PrioNet has available to
strengthen their research and training
experience.
PrioNet will be implementing a variety
of education and training programs to
facilitate learning exchange and enrich
the experience of students and young
professionals within the network. For
resources such as job postings and
training updates related to students
and young professionals, visit the Education
and Training link at
http://www.prionetcanada.ca. •
PrioNet's Research Projects Related to CWD & BSE
PrioNet Canada will address Canadian prion challenges through its five research themes. The
theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy
and Chronic Wasting Disease are outlined below:
Research Theme I: Bovine Spongiform Encephalopathy
Theme Leader: Dr. Steven Moore, University of Alberta
Associate Leader: Dr. Mike Belosevic, University of Alberta
Theme Pathologist: Dr. Stefanie Czub, Canadian Food Inspection Agency
A Comprehensive and Comparative Approach to Genetics & Pathobiology of Prion
Disease
Principal Investigator: Dr. Steven Moore, University of Alberta
Co-Investigators:
Dr. John Williams, Parco Tecnologico Padano, Italy
Dr. Michael Coulthart, Public Health Agency of Canada
Dr. Denny Crews, Agriculture & Agri-food Canada
Dr. Stefanie Czub, Canadian Food Inspection Agency
Dr. Michael Heaton, US Department of Agriculture
Prion Inactivation and Environment
Principal Investigator: Dr. Mike Belosevic, University of Alberta
Co-Investigators:
Dr. Norman Neumann, University of Calgary
Dr. Neil Cashman, University of British Columbia
Dr. Daniel Smith, University of Alberta
Dr. Steven Craik, University of Alberta
Dr. Mohamed Gamal El-Din, University of Alberta
Dr. Phillip Fedorak, University of Alberta
Immunoprophylaxis of Bovine Spongiform Encephalopathy
Principal Investigator: Dr. Andrew A. Potter, University of Saskatchewan
Co-Investigators:
Dr. Philip Griebel, University of Saskatchewan
Dr. Scott Napper, University of Saskatchewan
Dr. Lorne Babiuk, University of Saskatchewan
Research Theme II: Chronic Wasting Disease
Theme Leader: Dr. Ted Leighton, University of Saskatchewan
Associate Theme Leader: Dr. Cheryl Waldner, University of Saskatchewan
Sub-Theme Leader (for Scrapie): Dr. Aru Balachandran, Canadian Food Inspection Agency
Factors Affecting Prevalence and Geographic Spread of Chronic Wasting Disease in
Wild Deer in Saskatchewan (Phase I & II)
Principal Investigator: Dr. Trent Bollinger, University of Saskatchewan
Co-Investigators:
Dr. Dave Coltman, University of Alberta
Dr. Ted Leighton, Canadian Cooperative Wildlife Health Centre, University of Saskatchewan
Dr. Francois Messier, University of Saskatchewan
Dr. Cheryl Waldner, Western College of Veterinary Medicine, University of Saskatchewan
A Comparative Approach Examining Host Response to TSE Infection by Serial Analysis
of Gene Expression (microSAGE) in Cervids and Ovids
Principal Investigator: Dr. Stephen Moore, University of Alberta
Co-Investigators:
Dr. Michael Brownstein, J. Craig Venter Institute
Dr. Mike Miller, Wildlife Research Centre, Colorado
Dr. Catherine Graham, Canadian Food Inspection Agency
Dr. Aru Balachandran, Canadian Food Inspection Agency
PrioNet's Research Projects Related to CWD & BSE
PrioNet Canada will address Canadian prion challenges through its five research themes. The
theme leaders and targeted research projects related to the themes of Bovine Spongiform Encephalopathy
and Chronic Wasting Disease are outlined below:
Stay tuned to upcoming
issues of PrioNews as
we feature PrioNet's
three other research
themes:
==================================END
DNA polymorphisms of the prion doppel gene region in four different German
cattle breeds and cows tested positive for bovine spongiform encephalopathy
Journal Mammalian Genome
Publisher Springer New York
ISSN 0938-8990 (Print) 1432-1777 (Online)
Subject Biomedical and Life Sciences and Medicine
Issue Volume 16, Number 11 / November, 2005
DOI 10.1007/s00335-005-0052-9
Pages 884-892
Online Date Saturday, November 12, 2005
N. Balbus1, A. Humeny1, K. Kashkevich1, I. Henz1, C. Fischer2, C.-M. Becker1
and K. Schiebel1
(1) Institut für Biochemie, Emil-Fischer-Zentrum, Universität
Erlangen-Nürnberg, Fahrstrasse 17, 91054 , Erlangen, Germany
(2) Institut für Humangenetik, Universität Heidelberg, Im Neuenheimer Feld
366, 69120, Heidelberg, Germany
Received: 5 April 2005 Accepted: 18 July 2005 Published online: 11
November 2005
Abstract Polymorphisms of the prion protein gene PRNP have been shown to
influence the susceptibility/resistance to prion infections in human and
sheep. In addition, the T174M polymorphism within the flanking prion doppel
gene (PRND) was thought to be involved in susceptibility to sporadic
Creutzfeldt-Jacob disease. To study a possible influence of DNA
polymorphisms of the bovine PRND gene in bovine spongiform encephalopathy
(BSE), previously identified and newly isolated DNA polymorphisms were
genotyped in all available German cattle that tested positive for BSE.
Genotypes and calculated haplotypes were compared with breeding bulls
serving as controls. Analysis of the four major breeds Schwarzbunt (Holstein
Friesian), Rotbunt (Holstein Red), Fleckvieh (Simmental), and Braunvieh
(Swiss Brown) resulted in the isolation of the previously known
polymorphisms R50H and R132Q and two novel synonymous single nucleotide
polymorphisms (SNPs) C4820T and A5063T. Comparative genotype and haplotype
analysis of BSE and control animals revealed a significantly different
distribution of polymorphisms C4815T and R132Q in Fleckvieh animals but not
in the other breeds tested. No association to BSE susceptibility was
detectable for polymorphisms R50H and A5063T.
----------------------------------------------------------------------------
----
K. Schiebel
Email: [email protected]
Phone: 49-9131 85-26206
Fax: 49-9131 85-22485
References secured to subscribers.
http://www.springerlink.com/content/y12 ... abec8&pi=7
Subject: Atypical BSE in Germany-Proof of transmissibility and biochemical
characterization
Date: August 20, 2006 at 3:33 pm PST
Copyright © 2006 Elsevier B.V. All rights reserved.
Atypical BSE in Germany-Proof of transmissibility and biochemical
characterization
A. Buschmanna, A. Gretzschela, A.-G. Biacabeb, K. Schiebelc, C. Coronad, C.
Hoffmanna, M. Eidena, T. Baronb, C. Casaloned and Martin H. Groschupa, ,
aFriedrich-Loeffler-Institut (FLI), Institute for Novel and Emerging
Infectious Diseases, Boddenblick 5a, 17493 Greifswald, Insel Riems, Germany
bAFSSA-Lyon, Unite ATNC, Lyon, France
cInstitut für Biochemie, Universitity Erlangen-Nürnberg, Germany
dCEA, Instituto Zooprofilattico di Turino, Turin, Italy
Received 11 January 2006; revised 23 May 2006; accepted 2 June 2006.
Available online 17 August 2006.
Abstract
Intensive active surveillance has uncovered two atypical German BSE cases in
older cattle which resemble the two different atypical BSE phenotypes that
have recently been described in France (designated H-type) and Italy
(designated L-type or BASE). The H-type is characterized by a significantly
higher molecular size, but a conventional glycopattern of the proteinase K
treated abnormal prion protein (PrPSc), while the L-type PrPSc has only a
slightly lower molecular size and a distinctly different glycopattern. In
this paper we describe the successful transmission of both German atypical
BSE cases to transgenic mice overexpressing bovine PrPC. Upon challenge with
the L-type, these mice developed BSE after a substantially shorter
incubation period than any classical BSE transmission using these mice to
date. In contrast, the incubation period was distinctly prolonged when these
mice were challenged with the H-type. PrPSc accumulated in the brains of
these mice were of the same atypical BSE type that had been used for the
transmission. These atypical cases suggest the possible existence of
sporadic BSE cases in bovines. It is thus feasible that the BSE epidemic in
the UK could have also been initiated by an intraspecies transmission from a
sporadic BSE case.
Keywords: BSE; Cattle; PrPSc; Biochemical differentiation
http://www.sciencedirect.com/
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 280, NO. 45, pp. 37408–37414, November 11, 2005
© 2005 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A.
Bovine Prion Protein Gene (PRNP) Promoter Polymorphisms
Modulate PRNP Expression and May Be Responsible for
Differences in Bovine Spongiform Encephalopathy
Susceptibility*□S
Received for publication, June 10, 2005, and in revised form, July 20, 2005 Published, JBC Papers in Press, September 1, 2005, DOI 10.1074/jbc.M506361200
Petra Sander‡, Henning Hamann‡, Cord Dro¨gemu¨ ller‡, Kseniya Kashkevich§, Katrin Schiebel§, and Tosso Leeb‡1
From the ‡Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Bu¨nteweg 17p, 30559 Hannover, Germany
and the §Institute for Biochemistry, University of Erlangen-Nu¨rnberg, Fahrstrasse 17, 91054 Erlangen, Germany
The susceptibility of humans to the variant Creutzfeldt-Jakob
disease is greatly influenced by polymorphisms within the human
prion protein gene (PRNP). Similar genetic differences exist in
sheep, in which PRNP polymorphisms modify the susceptibility to
scrapie. However, the known coding polymorphisms within the
bovine PRNP gene have little or no effect on bovine spongiform
encephalopathy (BSE) susceptibility in cattle. We have recently
found a tentative association between PRNP promoter polymorphisms
and BSE susceptibility in German cattle (Sander, P.,
Hamann, H., Pfeiffer, I., Wemheuer, W., Brenig, B., Groschup, M.,
Ziegler, U., Distl, O., and Leeb, T. (2004) Neurogenetics 5, 19–25).A
plausible hypothesis explaining this observation could be that the
bovine PRNP promoter polymorphisms cause changes in PRNP
expression that might be responsible for differences in BSE incubation
time and/or BSE susceptibility. To test this hypothesis, we performed
a functional promoter analysis of the different bovine PRNP
promoter alleles by reporter gene assays in vitro and by measuring
PRNPmRNAlevels in calves with different PRNP genotypes in vivo.
Twovariable sites, a 23-bp insertion/deletion (indel) polymorphism
containing a RP58-binding site and a 12-bp indel polymorphism
containing an SP1-binding site, were investigated. Band shift assays
indicated differences in transcription factor binding to the different
alleles at the two polymorphisms. Reporter gene assays demonstrated
an interaction between the two postulated transcription factors and
lower expression levels of the ins/ins allele compared with the del/del
allele. The in vivo data revealed substantial individual variation of
PRNP expression in different tissues. In intestinal lymph nodes,
expression levels differed between the different PRNP genotypes. ...SNIP...END...TSS
