Immunohistochemical Detection and Distribution of Prion Protein in a Goat with Natural Scrapie

Abstract

Formalin-fixed, paraffin-embedded tissue sections from a 3-year-old female Angora goat suffering from clinical scrapie were immunostained after hydrated autoclaving using a monoclonal antibody (mAb, F99/97.6.1; IgG1) specific for a conserved epitope on the prion protein. Widespread and prominent deposition of the scrapie isoform of the prion protein (PrPSc) was observed in the brain, brainstem, spinal cord, retina, postganglionic neurons associated with parasympathetic ganglia of myenteric and submucosal plexuses, Peyer's patches, peripheral lymph nodes, and pharyngeal and palatine tonsils. The goat was homozygous for PrP alleles encoding 5 octapeptide repeat sequences in the N-terminal region of the prion protein and isoleucine at codon 142, a genotype associated with high susceptibility and short incubation times in goats. The results of this study indicate that mAb F99/97.6.1 is useful for detection of PrPSc deposition, and this is a specific and reliable immunohistochemical adjunct to histopathology for diagnosis of natural caprine scrapie, although precise determination of the diagnostic sensitivity and specificity of the assay as a diagnostic test for scrapie in goats will require examination of a sufficiently large sample size. As with ovine scrapie, prion protein is widely distributed in the central and peripheral nervous systems, gastrointestinal tract, and lymphoid tissues in natural caprine scrapie.

Atypical Scrapie in a Swiss Goat and Implications for Transmissible Spongiform Encephalopathy Surveillance

“…Widespread PrP sc deposition in the CNS and peripheral lymphoid tissues of a single naturally infected clinical scrapie goat was reported from the USA using IHC. 34 The immunostaining was found in all CNS areas showing degenerative changes, including various structures of the medulla oblongata and the cerebellum. Data from the UK 31 and Norway 10 indicate that the DMNV is the first structure in the brain where PrP sc augments to detectable amounts in the preclinical state of classical scrapie in sheep, but unfortunately similar investigations for goats are missing.…”

“…5 In the following decades the USA, 22,34 UK, 1,20 Canada, 32 Cyprus, 33 and Switzerland 13 reported similar caprine cases and confirmed clinical suspicious cases by histopathologic examination of the CNS. The distribution of histopathologic lesions within the CNS described in these naturally infected goats is generally in agreement with what has been described for naturally scrapie-affected sheep.…”

Detection of Disease-associated Prion Protein in the Optic Nerve and the Adrenal Gland of Cattle with Bovine Spongiform Encephalopathy by Using Highly Sensitive Immunolabeling Procedures

“…The granular pattern of immunolabeling in the cytoplasm of microglia and astrocytes seemed to be suggestive of lysosomes (Jeffrey et al 2000). Only weak immunolabeling has been detected in the optic nerves of sheep and goats with naturally occurring scrapie (Valdez et al 2003;Hortells et al 2006) and patients with sporadic and variant CJD (vCJD) (Head et al 2003), and in these instances, it seemed to be associated with oligodendrocytes or astrocytes. Although PrP Sc immunolabeling in the optic nerve appears to be associated with axon and secondary myelin loss in astrocytosis (Head et al 2003), axonal changes were undetectable in the present study.…”

Comparison of Immunohistochemistry and Two Rapid Tests for Detection of Abnormal Prion Protein in Different Brain Regions of Sheep with Typical Scrapie

“…11,12 In naturally infected sheep and goats, PrP sc may accumulate in all brain regions, but the distribution of PrP sc within the CNS may vary depending on the genotype or the scrapie strain, or both. 5,6 The medulla oblongata, at the level of the obex, is the target area of the CNS for scrapie diagnosis, but recently no PrP sc deposits in the obex of atypical scrapie cases have been described.…”