Scrapie agent proteins do not accumulate in grey tremor mice

The grey tremor mouse is an autosomal recessive mutant characterized by a phenotype of unusual pigmentation, neurological abnormalities and early death. These mice have a spongiform encephalopathy similar to scrapie and Creutzfeldt-Jakob disease. Although the disease is clearly heritable, the grey tremor mouse spongiform pathology has also been transmitted by inoculation of genetically normal mice with diseased brain homogenates. The possibility that a scrapie-like agent is involved has been proposed. We examined brain homogenates from grey tremor mice, scrapie-affected mice and normal mice for the presence of the mouse scrapie agent protein (MoSp33-37) and its normal cellular homologue. All untreated homogenates contained one or both isoforms of this protein as detected on immunoblots. Grey tremor mouse brain homogenates, when protease-treated, showed no evidence of MoSp33-37. A purification method for MoSp33-37 concentrated it in samples from scapie-affected mice, but this protein was not detected in grey tremor or normal mice. These results suggest that it is unlikely that the scrapie agent is involved in grey tremor disease.