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Review of mad goat disease
Prion gene from African wild goat

Mad Goat disease

Introduction [webmaster]: CSE [caprine spongiform encephalopathy] is the disease in goats corresponding to scrapie in sheep, kuru in humans, chronic wasting disease in deer, and so on.

Goats are not much of a quantitative issue in Britain, with 84,000 animals reared mainly for milk and hair versus an annual sheep slaughter of 19,000,000. In other countries, goats are much more abundant. There may be some use of goats in production of medical products. I found nothing one way or the other on dairy goat herds receiving protein supplements. Goats generally get thrown in with the sheep as far as offal regulations go.

Goats are said to be one of the three species known where TSE occurs naturally, with the disease going back 200 years or more. Goats are commonly kept with sheep, and CSE is associated with the occurence of OSE [scrapie]. In fact CSE is commonly assumed to be scrapie in goats, though no mechanism for horizontal cross-species transmission has been advanced. There has been a concern about BSE passing to goats mirroring the concern of BSE passing to sheep.

The genetic situation is a bit muddled. In the course of establishing various breeds, various prion alleles have become established that otherwise might be rare polymorphisms. While some breeds are prone to CSE or differ in incubation periods [codon 142], none of the alleles seems sufficient to cause CSE. [There is always the awful possibility, as in high hexapeptide-repeat chickens, that inbreeding has fixed a rogue prion with early onset of infectivity but very late onset of symptoms.]

In summmary, (non-experimental) CSE has been sporadic, not familial, just as with OSE and BSE. The wild-type goat prion sequence can be recovered with confidence since so many artiodactyl sequences are known.

It might be possible to demonstrate horizontal transmission more rigorously by putting goats into a (non-rendered protein supplemented) herd of sheep with a defined strain of scrapie, followed by strain-typing with comparison to inoculated goats, along with appropriate controls. The _mechanism_ of any horizontal transmission would not be illuminated by this experiment, however. The only possibly similar situation is chronic wasting disease in captive deer quartered in sheep pasture.

Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period.

J Gen Virol 77 ( Pt 11): 2885-2891 (1996) 
Goldmann W, Martin T, Foster J, Hughes S, Smith G, Hughes K, Dawson M, Hunter N
Age at disease onset and rate of progression of transmissible spongiform encephalopathies in man, sheep and mice are modulated by the host genome, in particular by the PrP gene and its allelic forms. Analysis of the caprine PrP gene revealed several different alleles. Four PrP protein variants were found, three of which were goat specific with single amino acid changes at codons 142, 143 and 240. The fourth was identical to the most common sheep PrP protein variant (Ala136-Arg154-Gln171). The dimorphism at codon 142 (Ile --> Met) appeared to be associated with differing disease incubation periods in goats experimentally infected with isolates of bovine spongiform encephalopathy, sheep scrapie CH1641 or sheep-passaged ME7 scrapie.

Encephalopathy in cattle experimentally infected with the scrapie agent.

Am J Vet Res 56 (5): 606-612 (1995) 
Clark WW, Hourrigan JL, Hadlow WJ
USDA, Animal and Plant Health Inspection Service, Veterinary Services, Mission, TX 78572, USA. 
Ten 8- to 10-month-old cattle were each inoculated intramuscularly, subcutaneously, intracerebrally, and orally with the scrapie agent to determine whether cattle are susceptible to it. Two inocula, both 10% homogenates of cerebrum, were used. One inoculum was from a sheep used for the second experimental ovine passage of the agent from 4 naturally affected Suffolk sheep. The other inoculum was from a goat used for the first experimental caprine passage of the agent from 2 naturally affected dairy goats living with the Suffolk sheep, the source of their infection. Between 27 and 48 months after inoculation, neurologic disease was observed in 1 of 5 cattle given the sheep brain homogenate and in 2 of 5 given the goat brain homogenate.

Transmission of bovine spongiform encephalopathy to sheep and goats.

Vet Rec 133 (14): 339-341 (1993) 
Foster JD, Hope J, Fraser H
Institute for Animal Health, AFRC, Edinburgh. 
Spongiform encephalopathy has been confirmed in both 'positive' and 'negative' lines of Cheviot sheep (selected for their differential response on experimental exposure to scrapie) after intracerebral injection or oral dosing with brain homogenate derived from cattle with bovine spongiform encephalopathy (BSE). With either challenge the incubation period of the disease ranged from 440 to 994 days in both lines of sheep. In a similar experiment, three Anglo-Nubian goats developed the disease 506 to 570 days after intracerebral infection with the same BSE homogenate, and two of three goats developed the disease 941 and 1501 days after oral dosing; the other goat and some sheep from each of the experimental groups remain alive 1720 days after exposure. This is the first report of the experimental transmission of BSE to sheep and goats.

Natural scrapie in goats: neuropathology.

Vet Rec 131 (5): 93-96 (1992) 
Wood JL, Done SH
Pathology Department, Central Veterinary Laboratory, Weybridge, Surrey.
The brains of the 20 goats affected with natural scrapie received at the Central Veterinary-Laboratory, Weybridge, since 1975 were examined microscopically. Lesions of a spongiform encephalopathy were found in the brainstem, cerebellum, diencephalon, corpus striatum, and also in the neopallium or cerebral cortex. The lesions in the neopallium have not previously been reported in natural scrapie in goats. Deposits of amyloid were present in the thalamus in three of the 20 goats.

CJD. Possible transmission to humans by consumption of wild animal brains.

 American Journal of  Medicine 1984 76 1 142-145 
 Kamin, M.; Patten, B. M. 
Although the natural mode of spread of the agent responsible for Creutzfeldt-Jakob disease is not known, several reports suggest transmission through eating contaminated food or brain. Four patients with Creutzfeldt-Jakob disease are described, who had a history of eating the brains of wild goat or squirrel. Those patients indicate the possible acquisition of Creutzfeldt-Jakob disease by ingestion of the agent from a presumptive reservoir in the central nervous system of wild animals.

Agent from squirrel causes brain illness

July 1, 1997
Herald Dispatch  Huntington, West Virginia
LEXINGTON, Ky. - A University of Kentucky researcher believes he may have found new information in the study of several brain-destroying illnesses that strike humans and animals. The illnesses are apparently transmitted by a mysterious agent unlike anything else found in nature.

Dr. Joseph Berger, chairman of UK's departmen of neurology, has discovered a common medical link in squirrel meat consumption in Kentucky, "mad cow" disease in England and a brain-destroying illness that afflicts cannibals in New Guinea. Berger stressed that he isn't suggesting people are putting themselves at risk by eating squirrel meat or that they should stop. "We need a lot more data."

Squirrel brains and CJD

Neurology Web-Forum
This response submitted by Bill Alford on 8/19/96.
Dr. Eric Weisman (a behavior neurologist) and myself have recently noted at least three patients who suddenly contracted CJD, and who admittedly had consumed the brains of squirrels. The findings were so revelent, that the University of Ky has requested the brains of 100 squirrels be submitted for examination and research. I had a patient that died secondarily of CJD - she was super productive weeks prior to her diagnosis, then vegitated for less than a month before her demise. A sad situation!!!

Transmissible virus dementia: evaluation of a zoonotic hypothesis.

Neuroepidemiology 1986;5(4):194-206 
Davanipour Z, Alter M, Sobel E, Asher DM, Gajdusek DC
Creutzfeldt-Jakob disease (CJD) and kuru are subacute transmissible dementing encephalopathies characterized by spongiform changes in the brain. Scrapie is a similar slow viral encephalopathy which affects sheep, goats and certain other animals. Anecdotal reports suggest that Creutzfeldt-Jakob disease could be a zoonosis. To evaluate the possibility that CJD is acquired from animals, a case-control study was conducted on 26 well-documented CJD cases and 40 controls. Data were collected on exposure to animals through occupations, hobbies, sports and pets. An excess exposure to certain animals was noted among the patients compared to controls in relation to occupation (deer, monkey, squirrel; odds ratio (OR) = 8.9; p less than 0.10) and hobbies (deer, OR = 9.0; rabbit, OR = 6.0; p less than 0.05). Similarly, exposure to animal organs was significantly greater in the CJD group (OR = 20.9; p less than 0.005). Statistically significant increased exposure to sheep or goats was not found among the patients. However, since spongiform encephalopathy has a wider host range than sheep and goats, the increased exposure to certain other animals suggests that a zoonotic source for CJD should be further explored.

Squirrel taxonomy: what kind of squirrels are we talking about?

Rodentia Sciurognathi Sciuridae Sciurinae 
                       Sciurus aberti (tassel-eared squirrel) 
                       Sciurus carolinensis (gray squirrel) 
                       Sciurus griseus 
                       Sciurus lis 
                       Sciurus niger (fox squirrel) 
                       Sciurus stramineus 
                       Sciurus vulgaris 

Detection of scrapie-associated fibrils in scrapie in goats.

Veterinary Record 1991 129 19 432 
Perrin, G. G.; Perrin, G. J.; Benoit, C.  
Three goats, 2 4-year-old sisters and the 3-year-old progeny of one of them were examined for wasting, fine head tremor and over-excitability triggered by noise. They all came from a flock in which scrapie had previously been suspected, but never confirmed. The animals were killed and brain samples cultured for Listeria were negative. Histopathology showed the presence of spongiform encephalopathy patterns as single and multiple vacuolisation of neuronal cytoplasm in the medulla. Electron microscopy revealed clusters of scrapie-associated fibrils.

British goat situation

ALICE THOMSON The Times: Britain: July 25 1996

More than 95 per cent of the 19 million sheep slaughtered each year already have their heads removed at the abattoir and sheep brain is not eaten in Britain except by some Muslim communities. Sheep's head soup is a traditional dish in the Outer Hebrides.

There are 84,000 goats in Britain, mainly reared for milk and hair, but a small market for goat meat has developed. Ruth Goodwin, of the British Goat Society, said: "Heads are not usually eaten. But we have just begun to get goat meat off the ground and this suggestion that BSE might get into goats is the last thing we need."

FDA proposes prohibiting sheep and goat offal in ruminant feed

A HREF="http://www.fda.gov/bbs/topics/VETNEWS/VET00051">VETNEWS ... 08/31/1994

In the August 29, 1994, Federal Register, FDA proposed a rule to prohibit specified offal from adult (more than 12 months of age) sheep and goats for use in ruminant feed. FDA is proposing this action because the specified offal may contain the agent that causes scrapie, a transmissible spongiform encephalopathy (TSE) of sheep and goats. ... Because FDA cannot positively rule out a direct association between scrapie, BSE, and human TSEs, FDA is proposing this action to protect the health of animals and humans.

Processed tissues from sheep and goats are used as ingredients in animal feeds. These products are derived from slaughter byproducts (slaughter inedibles) and dead, dying, diseased, and disabled (4-D) animals. These slaughter inedibles and 4-D animals include certain offal that are the subject of this proposed rule. Specified offal is defined in this proposal as any tissue from the brain, spinal cord, spleen, thymus, tonsil, lymph nodes, or intestines (duodenum to anus, inclusive) of sheep or goats, or any processed product that is reasonably expected to contain specified offal. Products which are likely to contain specified offal include dried meat solubles, glandular meal, meat meal, meat and bone meal, animal byproduct meal, meat meal tankage, animal digest, bone ash, bone charcoal, spent bone charcoal, cooked bone meal, and bone phosphate.....

Mapping of mitochondrial DNA of individual sheep and goats: rapid evolution in the D loop region.

Cell 11 (3): 571-583 (1977) 
Upholt WB, Dawid IB
Mitochondrial DNA (mtDNA) from sheep and goat was compared by restriction endonuclease analysis and heteroduplex mapping in the electron microscope. The fragment patterns produced by endonuclease Hae III from three individual sheep and two goat mtDNAs all differed from each other. The three sheep mtDNAs had identical Eco RI and Hind III fragments, but the two goat mtDNA patterns differed from each other as well as from sheep mtDNA. We estimate that each sheep mtDNA differs from each other by 0.5-1% of its nucleotide sequences, the two goat mtDNAs by 1-2%, and there is a 6-11% sequence difference between sheep and goat mtDNAs. [Ckhromosome count: cattle (Bos taurus, 2n = 60), goat (Capra hircus, 2n = 60) and sheep (Ovis aries, 2n = 54)

Allozyme divergence and phylogenetic relationships among Capra, Ovis and Rupicapra

Heredity (Edinburgh) 67 ( Pt 3): 281-286 (1991) 
Randi E, Fusco G, Lorenzini R, Toso S, Tosi G
Istituto Nazionale di Biologia della Selvaggina, Italy. 
Genetic divergence and phylogenetic relationships between the chamois (Rupicaprini, Rupicapra rupicapra rupicapra) and three species of the Caprini (Capra aegagrus hircus, Capra ibex ibex and Ovis ammon musimon) have been studied by multilocus protein electrophoresis. Dendrograms have been constructed both with distance and parsimony methods. Goat, sheep and chamois pair-wise genetic distances had very similar values. All the topologies showed that Capra, Ovis and Rupicapra originate from the same internode, suggesting the hypothesis of a common, and almost contemporaneous, ancestor. The estimated divergence times among the three genera ranged from 5.28 to 7.08 Myr. These findings suggest the need to reconsider the evolutionary relationships in the Capriae.

http://http2.brunel.ac.uk:8080/~hssrsdn/bse/tse-refs.htm

  FOSTER, JD;HOPE, J;MCCONNELL, I;BRUCE, M;FRASER, H (1994). 
Transmission of bovine spongiform encephalopathy to sheep, goats
Veterinary Record  133(14): 339-341

Prion gene from African wild goat

Spongiform central nervous system myelinopathy in African dwarf goats.
Obermaier G, Kretzschmar HA, Hafner A, Heubeck D, Dahme E
General Pathology and Neuropathology, Ludwig-Maximilians-University, Munich, Germany.
J Comp Pathol 113 (4): 357-372 (1995)
"A novel spongiform myelinopathy of the central nervous system (CNS) of eleven African dwarf goats (Caprus hircus aegagrus) was examined by light and electron microscopy. Histological lesions consisted of extensive vacuolation predominantly of the white matter of the diencephalon, midbrain and cerebellar peduncles, as well as of spinal white matter. Ultrastructurally, vacuoles were shown to be intramyelinic, resulting from the splitting of the outer myelin lamellae at the intraperiod line. A few oligodendrocytes showed vacuolar degeneration of cell bodies and processes. Inflammatory reactions were absent. The observed lesions point to an unknown primary damage of oligodendroglia and central myelin. A hereditary background of the disorder is suspected as all investigated dwarf goats were half-brothers or -sisters and partly descended from the mating of adult females with their own sire."

Dwarf goat prion differs from regular goat in 1 position, met143ile; from cow at Q190E, I209M, P241S; from human in 8 positions. While these differences are already small and conservative, note that the putative infectious core domain up through helix 1 of dwarf goat is practically identical with human. From the familial CJD truncation mutant Y145stop, this domain may be central to the cross-species transmission coefficient.

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