Transmissible spongiform encephalopathy in the gray tremor mutant mouse

Area of Science:

• Neuroscience
• Genetics
• Pathology

Background:

• Gray tremor (gt) is an autosomal recessive mutation in mice affecting pigmentation, neurological function, and causing early death.
• The gt mutation leads to hypo- and dysmyelination and spongiform encephalopathy, mimicking unconventional transmissible agents.
• Heterozygotes (+/gt) develop mild spongiform encephalopathy later in life.

Purpose of the Study:

• To investigate the nature of the spongiform encephalopathy in the gray tremor mouse mutant.
• To determine if the spongiform changes are transmissible to genetically normal mice.

Main Methods:

• A transmission experiment was conducted using neonatal mice inoculated intracerebrally with gt/gt brain homogenate.
• Genetically normal mice of three strains (BALB/cBy, C3HeB/FeJ, C57BL/6J) were monitored after inoculation.
• Surviving mice were analyzed for spongiform changes at a long post-inoculation interval (682-721 days).

Main Results:

• Neonatal inoculation of normal mice with gt/gt brain homogenate induced spongiform changes.
• These induced spongiform changes were histopathologically similar to those observed in the gray tremor mutant.
• All surviving mice across three strains developed the characteristic spongiform changes.

Conclusions:

• The gray tremor mutation results in a naturally occurring spongiform encephalopathy.
• The study demonstrates the transmissibility of this spongiform encephalopathy to genetically normal mice.
• The findings suggest that the expression of the gray tremor phenotype involves an interaction between genetic factors and a transmissible agent.