Analysis of CAG trinucleotide repeats from mouse cDNA sequences.

A number of human single gene disorders are now known to result from abnormal expansion of trinucleotide repeats. Spinal muscular bulbar atrophy, myotonic dystrophy, Huntington's Disease, spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy are all caused by expansions of CAG repeats. Abnormal expansion of trinucleotide repeats has only so far been described in humans, and no mouse models exist for these diseases. In order to investigate trinucleotide repeat stability in mice, the Genbank and EMBL nucleotide databases were screened to find genes containing CAG repeats. Of the sequences selected, 32 were from mouse, and in 12 of these the repeat was in transcribed sequence and contained at least seven perfect repeats. These repeats were then analysed by PCR to evaluate the degree of variability of repeat length in the various genes. Two of the genes containing variable length CAG repeats, seven in absentia homologue 1b (Sinh1b), and choline acetyl transferase (Chat), which had not previously been mapped in the mouse genome, were mapped by linkage analysis in an interspecific backcross. Sinh1b maps very distally on the X chromosome, and Chat maps to chromosome 14.