Mice with Mutations in the Mahogany Gene Atrn Have Cerebral Spongiform Changes

A new mutation characterized by mahogany coat color, sprawling gait, tremors, and severe vacuolization of cerebrum, brainstem, granular layer of cerebellum and spinal cord was discovered in a stock of Mus castaneus mice. Tests for allelism using mice homozygous for 2 known mahogany attractin (Atrn) mutants showed that the new mutation was an allele of Atrn. Northern analysis showed no expression of Atrn in the new mutants. Southern analysis strongly suggested that the new mutation deleted most of the Atrn gene, but was not large enough to affect flanking genes including the prion gene, Prnp, located 1.1 cM from Atrn on Chromosome 2. Histopathological analysis of brains from each of the 2 known Atrn mutants showed that they also have severe spongiform changes. This finding was surprising and raises questions about the mechanism by which mahogany controls appetite and metabolic rate, as recently reported.

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