Open AccessTransmissible spongiform encephalopathy in the gray tremor mutant mouse.
Author(s) -
Richard L. Sidman,
Hannah C. Kinney,
Hope O. Sweet
Publication year - 1985
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.82.1.253
Subject(s) - mutant , biology , bovine spongiform encephalopathy , phenotype , encephalopathy , virology , locus (genetics) , heterozygote advantage , transmissible spongiform encephalopathy , mutation , genetics , scrapie , pathology , allele , medicine , prion protein , gene , disease
Gray tremor (gt) is an autosomal recessive mutation in the mouse linked to caracul (Ca) on chromosome 15. The complex mutant phenotype includes pigmentation defects, tremor, seizures, hypo- and dysmyelination in central and peripheral nervous systems, spongiform encephalopathy, and early death. The heterozygote (+/gt) is phenotypically normal but develops a mild spongiform encephalopathy from 2 months of age onward. The pigmentation and myelination disorders indicate that the gt genetic locus is active neonatally and probably earlier. This report focuses mainly on the later-expressed vacuolating disorder, which most closely mimics in tissue distribution, histopathology, and ultrastructure the spongiform encephalopathies caused by unconventional transmissible agents. This lesion was produced in genetically normal mice in a transmission experiment: of 99 neonatal mice inoculated intracerebrally with gt/gt brain homogenate, all 7 mice of three strains (BALB/cBy, C3HeB/FeJ, and C57BL/6J) allowed to survive for the unusually long interval of 682-721 days after inoculation, developed spongiform changes distributed as in the mutant phenotype. The gray tremor mutant presents a naturally occurring spongiform encephalopathy whose expression is determined by the interaction of genetic factors and a transmissible agent.