scholarly journals Passage of chronic wasting disease prion into transgenic mice expressing Rocky Mountain elk (Cervus elaphus nelsoni) PrPC

2006 ◽  
Vol 87 (12) ◽  
pp. 3773-3780 ◽  
Author(s):  
Giuseppe LaFauci ◽  
Richard I. Carp ◽  
Harry C. Meeker ◽  
Xuemin Ye ◽  
Jae I. Kim ◽  
...  
Keyword(s):  
Cervus Elaphus ◽  
Incubation Time ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Rocky Mountain ◽  
Intracerebral Injection ◽  
Wasting Disease ◽  
Transgenic Mouse Line ◽  
Cervus Elaphus Nelsoni ◽  
Canadian Provinces

Chronic wasting disease (CWD) of elk (Cervus elaphus nelsoni) and mule deer (Odocoileus hemionus) is one of three naturally occurring forms of prion disease, the others being Creutzfeldt–Jakob disease in humans and scrapie in sheep. In the last few decades, CWD has spread among captive and free-ranging cervids in 13 US states, two Canadian provinces and recently in Korea. The origin of the CWD agent(s) in cervids is not known. This study describes the development of a transgenic mouse line (TgElk) homozygous for a transgene array encoding the elk prion protein (PrPC) and its use in propagating and simulating CWD in mice. Intracerebral injection of one mule deer and three elk CWD isolates into TgElk mice led to disease with incubation periods of 127 and 95 days, respectively. Upon secondary passage, the incubation time was reduced to 108 and 90 days, respectively. Upon passage into TgElk mice, CWD prions (PrPSc) maintained the characteristic Western blot profiles seen in CWD-affected mule deer and elk and produced histopathological modifications consistent with those observed in the natural disease. The short incubation time observed on passage from cervid to mouse with both mule deer and elk CWD brain homogenates and the demonstrated capacity of the animals to propagate (mouse to mouse) CWD agents make the TgElk line a valuable model to study CWD agents in cervid populations. In addition, these results with this new transgenic line suggest the intriguing hypothesis that there could be more than one strain of CWD agent in cervids.

scholarly journals Detection of PrPCWDin Postmortem Rectal Lymphoid Tissues in Rocky Mountain Elk (Cervus Elaphus Nelsoni) Infected with Chronic Wasting Disease

2006 ◽  
Vol 18 (6) ◽  
pp. 553-557 ◽  
Author(s):  
Terry R. Spraker ◽  
Thomas L. Gidlewski ◽  
Aru Balachandran ◽  
Kurt C. VerCauteren ◽  
Lynn Creekmore ◽  
...  
Keyword(s):  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Rocky Mountain ◽  
Lymphoid Tissues ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni ◽  
Rocky Mountain Elk

scholarly journals Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease

2006 ◽  
Vol 87 (11) ◽  
pp. 3443-3450 ◽  
Author(s):  
Jean E. Jewell ◽  
Jeremy Brown ◽  
Terry Kreeger ◽  
Elizabeth S. Williams
Keyword(s):  
Western Blot ◽  
Odocoileus Virginianus ◽  
Prion Protein ◽  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Striated Muscle ◽  
Mule Deer ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni

To investigate the possible presence of disease-associated prion protein (PrPd) in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western immunoblot and immunohistochemistry (IHC). PrPd was detected in samples of heart muscle from seven of 16 CWD-infected white-tailed deer, including one free-ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer samples, nor in the single CWD-infected moose. For white-tailed deer, PrPd was detected by Western blot at multiple sites throughout the heart; IHC results on ventricular sections of both elk and white-tailed deer showed positive staining in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of PrPd in cardiac tissues were estimated from Western blot band intensity to be lower than levels found in brain tissue. PrPd was not detected in diaphragm, triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of the study subjects. This is the first report of PrPd in cardiac tissue from transmissible spongiform encephalopathy-infected ruminants in the human food chain and the first demonstration by immunological assays of PrPd in any striated muscle of CWD-infected cervids.

Neuropathology of Chronic Wasting Disease of Mule Deer (Odocoileus hemionus) and Elk (Cervus elaphus nelsoni)

1993 ◽  
Vol 30 (1) ◽  
pp. 36-45 ◽  
Author(s):  
E. S. Williams ◽  
S. Young
Keyword(s):  
Bovine Spongiform Encephalopathy ◽  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Neuronal Degeneration ◽  
Mule Deer ◽  
Amyloid Plaques ◽  
Odocoileus Hemionus ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni

The pathology of the central nervous system of nine mule deer ( Odocoileus hemionus) and six elk ( Cervus elaphus nelsoni) with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. Lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of significant inflammatory response. Distribution and severity of lesions were evaluated at 57 locations; there were only minor differences between deer and elk. Consistent, severe lesions occurred in olfactory tubercle and cortex, hypothalamus, and the parasympathetic vagal nucleus of deer, and sections examined from these regions would be sufficient to establish a diagnosis of chronic wasting disease. Lesions were milder in these locations in elk but were sufficiently apparent to be of diagnostic value. Other differences included increased severity of lesions in some thalamic nuclei in elk in contrast to deer, the occurrence of amyloid plaques demonstrable by hematoxylin and eosin and histochemical stains in deer in contrast to elk, and the presence of mild white matter lesions in elk but not in deer. Lesions of chronic wasting disease were qualitatively comparable to those of scrapie, bovine spongiform encephalopathy, transmissible mink encephalopathy, and the human spongiform encephalopathies. Topographic distribution and lesion severity of chronic wasting disease were most similar to those of scrapie and bovine spongiform encephalopathy. Duration of clinical disease did not significantly influence lesion distribution or severity in either species.

scholarly journals Progressive accumulation of the abnormal conformer of the prion protein and spongiform encephalopathy in the obex of nonsymptomatic and symptomatic Rocky Mountain elk (Cervus elaphus nelsoni) with chronic wasting disease

2015 ◽  
Vol 27 (4) ◽  
pp. 431-441 ◽  
Author(s):  
Terry R. Spraker ◽  
Thomas Gidlewski ◽  
Jenny G. Powers ◽  
Tracy Nichols ◽  
Aru Balachandran ◽  
...  
Keyword(s):  
Prion Protein ◽  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Rocky Mountain ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni ◽  
Single Section ◽  
Spongiform Degeneration ◽  
Rocky Mountain Elk ◽  
Progressive Accumulation

The purpose of our study was to describe the progressive accumulation of the abnormal conformer of the prion protein (PrPCWD) and spongiform degeneration in a single section of brain stem in Rocky Mountain elk ( Cervus elaphus nelsoni) with chronic wasting disease (CWD). A section of obex from 85 CWD-positive elk was scored using the presence and abundance of PrPCWD immunoreactivity and spongiform degeneration in 10 nuclear regions and the presence and abundance of PrPCWD in 10 axonal tracts, the subependymal area of the fourth ventricle, and the thin subpial astrocytic layer (glial limitans). Data was placed in a formula to generate an overall obex score. Data suggests that PrPCWD immunoreactivity and spongiform degeneration has a unique and relatively consistent pattern of progression throughout a section of obex. This scoring technique utilizing a single section of obex may prove useful in future work for estimating the presence and abundance of PrPCWD in peripheral tissues and the nervous system in elk with CWD.

Field Validation and Assessment of an Enzyme-Linked Immunosorbent Assay for Detecting Chronic Wasting Disease in Mule Deer (Odocoileus Hemionus), White-Tailed Deer (Odocoileus Virginianus), and Rocky Mountain Elk (Cervus Elaphus Nelsoni)

2003 ◽  
Vol 15 (4) ◽  
pp. 311-319 ◽  
Author(s):  
Charles P. Hibler ◽  
Kathi L. Wilson ◽  
Terry R. Spraker ◽  
Michael W. Miller ◽  
Robert R. Zink ◽  
...  
Keyword(s):  
Cervus Elaphus ◽  
Mule Deer ◽  
Rocky Mountain ◽  
Odocoileus Hemionus ◽  
Field Application ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wasting Disease ◽  
Tissue Samples ◽  
Validation Phase ◽  
Cervus Elaphus Nelsoni

Tissue samples ( n = 25,050 total) from 23,256 mule deer ( Odocoileus hemionus), Rocky Mountain elk ( Cervus elaphus nelsoni), and white-tailed deer ( Odocoileus virginianus) collected statewide in Colorado were examined for chronic wasting disease (CWD) using an enzyme-linked immunosorbent assay developed by Bio-Rad Laboratories, Inc. (brELISA), in a 2-phase study. In the validation phase of this study, a total of 4,175 retropharyngeal lymph nodes (RLN) or obex (OB) tissue samples were examined independently by brELISA and immunohistochemistry (IHC). There were 137 IHC-positive samples and 4,038 IHC-negative samples. Optical density (OD) values from brELISA were classified as “not detected” or “suspect” based on recommended cutoff values during the validation phase. Using IHC-positive cases as known CWD-infected individuals and assuming IHC-negative cases as uninfected, the relative sensitivity of brELISA depending on species ranged from 98.3% to 100% for RLN samples and 92.1% to 93.3% for OB samples; the relative specificity of brELISA depending on species ranged from 99.9% to 100% for RLN samples and was 100% for OB samples. Overall agreement between brELISA and IHC was ≥97.6% in RLN samples and ≥95.7% in OB samples of all species where values could be calculated; moreover, mean brELISA OD values were ≥46× higher in IHC-positive samples than in IHC-negative samples. Discrepancies were observed only in early-stage cases of CWD. Based on the validation phase data, only RLN samples were collected for the field application phase of this study and only samples with brELISA OD values ≤0.1 were examined by IHC. Among 20,875 RLN samples screened with brELISA during this second testing phase, 155 of 8,877 mule deer, 33 of 11,731 elk, and 9 of 267 white-tailed deer samples (197 total) had OD values ≤0.1 and were further evaluated by IHC to confirm evidence of CWD infection. Of cases flagged for IHC follow-up, 143 of 155 mule deer, 29 of 33 elk, and all 9 white-tailed deer were confirmed positive. Mean (±SE) OD values for IHC-positive cases detected during the field application phase were comparable with those measured in RLN tissues during the validation phase. Based on these data, brELISA was determined to be an excellent rapid test for screening large numbers of samples in surveys designed to detect CWD infections in deer and elk populations.

EFFICACY OF ANTEMORTEM RECTAL BIOPSIES TO DIAGNOSE AND ESTIMATE PREVALENCE OF CHRONIC WASTING DISEASE IN FREE-RANGING COW ELK (CERVUS ELAPHUS NELSONI)

2013 ◽  
Vol 49 (2) ◽  
pp. 270-278 ◽  
Author(s):  
Ryan J. Monello ◽  
Jenny G. Powers ◽  
N. Thompson Hobbs ◽  
Terry R. Spraker ◽  
Katherine I. O’Rourke ◽  
...  
Keyword(s):  
Cervus Elaphus ◽  
Chronic Wasting Disease ◽  
Wasting Disease ◽  
Cervus Elaphus Nelsoni ◽  
Rectal Biopsies ◽  
Estimate Prevalence ◽  
Free Ranging

scholarly journals PrP genotypes of free-ranging wapiti (Cervus elaphus nelsoni) with chronic wasting disease

2008 ◽  
Vol 89 (5) ◽  
pp. 1324-1328 ◽  
Author(s):  
Matteo Perucchini ◽  
Karen Griffin ◽  
Michael W. Miller ◽  
Wilfred Goldmann
Keyword(s):  
Cervus Elaphus ◽  
Gene Sequence ◽  
Chronic Wasting Disease ◽  
Wasting Disease ◽  
Susceptibility To Infection ◽  
Cervus Elaphus Nelsoni ◽  
Naturally Occurring ◽  
Genotype Frequencies ◽  
The Family ◽  
Free Ranging

Variation in PrP prion gene sequence appears to modulate susceptibility to chronic wasting disease (CWD), a naturally occurring prion disease affecting four North American species of the family Cervidae. Wapiti (Cervus elaphus nelsoni) PrP is polymorphic at codon 132 [methionine (M) or leucine (L)]. We genotyped 171 samples, collected between 2002 and 2005 from CWD-infected and uninfected wapiti from three free-ranging populations in Colorado, USA, to study influences of PrP polymorphisms on CWD susceptibility further. Overall genotype frequencies for 124 apparently uninfected animals were 65.3 % MM132, 32.3 % ML132 and 2.4 % LL132; for 47 CWD-infected animals, these frequencies were 70.2 % MM132, 27.7 % ML132 and 2.1 % LL132. Surprisingly, our data revealed that, among recent (approx. 2002–2005) CWD cases detected in free-ranging Colorado wapiti, the three PrP codon 132 genotypes were represented in proportion to their abundance in sampled populations (P≥0.24) and all three genotypes showed equivalent susceptibility to infection.

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