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oux c simon s padilla d benestad s l lantier f schelcher f grassi j torres j m umr inra envt 1225 ecole nationale veterinaire de toulouse france icisa inla madrid spain cea ibitec 5 dsv cea saclay gif sur yvette cedex france national veterinary institute postboks 750 sentrum 0106 oslo norway inra iasp centre inra de tours 3738o nouzilly france content atypical scrapie is a tse occurring in small ruminants and harbouring peculiar clinical epidemiological and biochemical properties currently this form of disease is identified in a large number of countries in this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice tg expressing different species prp sequence the donor isolate was collected in 1995 in a french commercial sheep flock inoculation into ahq ahq sheep induced a disease which had all neuro pathological and biochemical characteristics of atypical scrapie transmitted into transgenic mice expressing either ovine or prpc the isolate retained all the described characteristics of atypical scrapie surprisingly the tse agent characteristics were dramatically different v hen passaged into tg bovine mice the recovered tse agent had biological and biochemical characteristics similar to those of atypical bse l in the same mouse model moreover whereas no other tse agent than bse were shown to transmit into tg porcine mice atypical scrapie was able to develop into this model albeit with low attack rate on first passage furthermore after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than bse adapted to this porcine mouse model altogether these data indicate i the unsuspected potential abilities of atypical scrapie to cross species barriers ii the possible capacity of this agent to acquire new characteristics when crossing species barrier these findings raise some interrogation on the concept of tse strain and on the origin of the diversity of the tse agents and could have consequences on field tse control measures http www neuroprion org resources pdf_docs conferences prion2008 abstract book prion2008 pdf friday february 11 2011 atypical nor98 scrapie infectivity in sheep peripheral tissues http nor 98 blogspot com 2011 02 atypicalnor98 scrapie infectivity in html research emerging infectious diseases www cdc gov eid vol 17 no 5 may 2011 experimental oral transmission of atypical scrapie to sheep marion m simmons s jo moore 1 timm konold lisa thurston linda a terry leigh thorne richard lockey chris vickery stephen a c hawkins melanie j chaplin and john spiropoulos to investigate the possibility of oral transmission of atypical scrapie in sheep and determine the distribution of infectivity in the animals peripheral tissues we challenged neonatal lambs orally with atypical scrapie they were then killed at 12 or 24 months screening test results were negative for disease specifi c prion protein in all but 2 recipients they had positive results for examination of brain but negative for peripheral tissues infectivity of brain distal ileum and spleen from all animals was assessed in mouse bioassays positive results were obtained from tissues that had negative results on screening these fi ndings demonstrate that atypical scrapie can be transmitted orally and indicate that it has the potential for natural transmission and iatrogenic spread through animal feed detection of infectivity in tissues negative by current surveillance methods indicates that diagnostic sensitivity is suboptimal for atypical scrapie and potentially infectious material may be able to pass into the human food chain snip although we do not have epidemiologic evidence that supports the effi cient spread of disease in the fi eld these data imply that disease is potentially transmissible under fi eld situations and that spread through animal feed may be possible if the current feed restrictions were to be relaxed additionally almost no data are available on the potential for atypical scrapie to transmit to other food animal species certainly by the oral route however work with transgenic mice has demonstrated the potential susceptibility of pigs with the disturbing fi nding that the biochemical properties of the resulting prpsc have changed on transmission 40 the implications of this observation for subsequent transmission and host target range are currently unknown how reassuring is this absence of detectable prpsc from a public health perspective the bioassays performed in this study are not titrations so the infectious load of the positive gut tissues cannot be quantifi ed although infectivity has been shown unequivocally no experimental data are currently available on the zoonotic potential of atypical scrapie either through experimental challenge of humanized mice or any meaningful epidemiologic correlation with human forms of tse however the detection of infectivity in the distal ileum of animals as young as 12 months in which all the tissues tested were negative for prpsc by the currently available screening and confi rmatory diagnostic tests indicates that the diagnostic sensitivity of current surveillance methods is suboptimal for detecting atypical scrapie and that potentially infectious material may be able to pass into the human food chain undetected emerging infectious diseases www cdc gov eid vol 17 no 5 may 2011 http wwwnc cdc gov eid article 17 5 pdfs 10 1654 pdf identifying variation in the u s bovine prion gene bovine spongiform encephalopathy bse or mad cow disease is a serious threat to the u s beef industry while the first confirmed case of bse on u s soil in december 2003 had little effect on domestic consumption it carved into our international beef sales according to usda s economic research service the united states exported only 552 million worth of beef in 2004 down from 2 6 billion in 2002 and 3 1 billion in 2003 a reduction due in part to the bse case are some cattle more susceptible to bse is there a genetic component involved to address these and other questions ars scientists at the u s meat animal research center usmarc at clay center nebraska have sequenced the bovine prion gene prnp in 192 cattle representing 16 beef and 5 dairy breeds common in the united states this work was partially funded by a grant from usda s cooperative state research education and extension service prions are proteins that occur naturally in mammals bse is a fatal neurological disorder characterized by irregularly folded prions much is unknown about the disease but scientists recognize a correlation between variations in the prnp gene in some mammals and susceptibility to transmissible spongiform encephalopathies such as scrapie in sheep evidence indicates that this could also be true in cattle says molecular biologist mike clawson he is among the usmarc scientists examining prnp variation to learn if and how different forms or alleles of the prion gene correlate with bse susceptibility a thorough characterization of prnp variation in a u s cattle population will provide a reference framework for researchers to use in analyzing prnp sequences from cattle afflicted with bse from the 192 prnp genes sequenced clawson and his colleagues have identified 388 variations or polymorphisms of which 287 were previously unknown some of these polymorphisms may influence bse susceptibility in cattle he says ongoing studies with european collaborators are testing the newly identified variants for association with bse if these studies show some cattle to be genetically less susceptible to the disease this information could shed light on bse s transmission and development the united states has had only three confirmed cases of bse laboratory tests showed that the second and third of these appear to differ significantly from the first case says clawson by comparing the prnp sequence from bse infected cattle to healthy cattle we may be able to identify genetic markers in the prion gene that predict bse susceptibility he says in addition to prnp the team is currently sequencing several genes closely related to it these too will be tested for their association with bse the prevalence of bse in the united states is extremely low and is declining worldwide clawson says well characterized genetic markers that correlate to resistance could improve our understanding of the disease and prepare the cattle industry to respond if another prion disease arises in the future by laura mcginnis agricultural research service information staff this research is part of animal health an ars national program 103 described on the world wide web at www nps ars usda gov michael l clawson is at the usda ars roman l hruska u s meat animal research center p o box 166 clay center ne 68933 phone 402 762 4342 fax 402 762 4375 identifying variation in the u s bovine prion gene was published in the january 2007 issue of agricultural research magazine http seprl ars usda gov is ar archive jan07 bovine0107 htm pf 1 research project susceptibility of cattle with the e211k prnp allele to bse location virus and prion research unit project number 3625 32000 086 14 project type specific cooperative agreement start date aug 14 2008 end date jul 31 2013 objective the objective of this cooperative research project is to investigate the influence of the bovine prnp gene polymorphisms e211k on the susceptibility to bse specifically the research project will provide 134 embryos that will be used to generate approximately 62 animals 31 of which will contain the rare allele for the purposes bse research this ongoing sca with iowa state university to produce cattle with the e211k prnp allele for bse research has resulted in an e211 k211 heterozygous bull we are now in the unique position to extend our research on this allele to include animals homozygous for k at position 211 based upon our understanding of this novel polymorphism one would predict homozygotes would have a more rapid onset of clinical signs associated with genetic bse than heterozygotes approach to achieve the research goals it is imperative to increase the number of animals available to study this prnp polymorphism one female calf of the 2006 bse case was identified and carries the e211k allele the specific objectives are to be accomplished through the production of multiple offspring from this e211k heifer through superovulation and embryo transfer approximately 50 of the offspring will be heterozygous for the e211k polymorphism while the others will serve as genetically matched non e211k controls collection of semen from an e211k heterozygous bull will allow creation of e211k homozygotes to protect this unique resource immediate collection of embryos is necessary the initial goal is to harvest 134 embryos that should result in approximately 62 pregnancies half of which will carry the e211k polymorphism for immediate use in the studies to amplify the e211k material test for genetic susceptibility to tse and develop a breeding group to produce calves for transmissibility studies to achieve the goal of understanding the role of the e211k polymorphism with regard to genetic bse we have utilized superovulation and embryo transfer obtaining a e211 k211 containing bull we are now in a position to collect semen from the e211 k211 heterozygous bull to create k211 k211 homozygotes to accomplish this goal we plan to collect semen from this bull and through artificial insemination using semen from the e211 k211 bull with superovulation and embryo transplantation using other e211 k211 heterzygotes generate 30 40 embryos resulting in 15 20 pregnancies yielding approximately 5 k211 k211 homozygous animals and 10 e211 k211 heterozyous animals as well as 5 e211 e211 homozygous controls http www ars usda gov research projects projects htm accn_no 413249 http www cdc gov eid content 15 12 pdfs 2013 pdf subject identifying variation in the u s bovine prion gene date january 22 2007 at 8 32 am pst identifying variation in the u s bovine prion gene by laura mcginnis january 22 2007 do genes affect bovine spongiform encephalopathy also known as bse or mad cow disease are some cattle more susceptible than others to address these and other questions agricultural research service ars scientists at the u s meat animal research center in clay center neb have sequenced the bovine prion gene prnp in 192 cattle that represent 16 beef and five dairy breeds common in the united states this work partially funded by a grant from the u s department of agriculture s cooperative state research education and extension service is expanding the understanding of how the disease works bse is a fatal neurological disorder characterized by prions proteins that occur naturally in mammals that fold irregularly molecular biologist mike clawson and his clay center colleagues are examining prnp variation in order to learn if and how prions correlate with bse susceptibility from the 192 prnp sequences clawson and his colleagues have identified 388 variations or polymorphisms 287 of which were previously unknown some of these polymorphisms may influence bse susceptibility in cattle comparing prnp sequences from infected and healthy cattle may enable researchers to identify genetic markers in the prion gene that predict bse susceptibility in addition to prnp the team is currently sequencing several closely related genes which will also be tested for their association with bse the prevalence of bse in the united states is extremely low but this research could improve understanding of the disease and prepare the cattle industry to respond if another prion disease should arise in the future http www ars usda gov is pr 2007 070122 htm identifying variation in the u s bovine prion gene bovine spongiform encephalopathy bse or mad cow disease is a serious threat to the u s beef industry while the first confirmed case of bse on u s soil in december 2003 had little effect on domestic consumption it carved into our international beef sales according to usdas economic research service the united states exported only 552 million worth of beef in 2004 down from 2 6 billion in 2002 and 3 1 billion in 2003 a reduction due in part to the bse case are some cattle more susceptible to bse is there a genetic component involved to address these and other questions ars scientists at the u s meat animal research center usmarc at clay center nebraska have sequenced the bovine prion gene prnp in 192 cattle representing 16 beef and 5 dairy breeds common in the united states this work was partially funded by a grant from usda s cooperative state research education and extension service prions are proteins that occur naturally in mammals bse is a fatal neurological disorder characterized by irregularly folded prions much is unknown about the disease but scientists recognize a correlation between variations in the prnp gene in some mammals and susceptibility to transmissible spongiform en...