The DST gene in neurobiology.

Abstract

DST is a gene whose alternative splicing yields epithelial, neuronal, and muscular isoforms. The autosomal recessive Dst^dt (dystonia musculorum) spontaneous mouse mutation causes degeneration of spinocerebellar tracts as well as peripheral sensory nerves, dorsal root ganglia, and cranial nerve ganglia. In addition to Dst^dt mutants, axonopathy and neurofilament accumulation in perikarya are features of two other murine lines with spontaneous Dst mutations, targeted Dst knockout mice, DstTg4 transgenic mice carrying two deleted Dst exons, Dst^Gt mice with trapped actin-binding domain-containing isoforms, and conditional Schwann cell-specific Dst knockout mice. As a result of nerve damage, Dst^dt mutants display dystonia and ataxia, as seen in several genetically modified models and their motor coordination deficits have been quantified along with the spontaneous Dst nonsense mutant, the conditional Schwann cell-specific Dst knockout, the conditional Dst^Gt mutant, and the Dst-b isoform specific Dst mutant. Recent findings in humans have associated DST mutations of the Dst-b isoform with hereditary sensory and autonomic neuropathies type 6 (HSAN-VI). These data should further encourage the development of genetic techniques to treat or prevent ataxic and dystonic symptoms.