MOLECULAR-GENETIC DISSECTION OF MOUSE UNCONVENTIONAL MYOSIN-VA - HEADREGION MUTATIONS

The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). M ice carrying null alleles of dilute have a lightened coat color and di e from a neurological disorder resembling ataxia and opisthotonus with in three weeks of birth. Immunological and ultrastructural studies sug gest that MyoVA is involved in the transport of melanosomes in melanoc ytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing appro ach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seve n of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were us ed to predict how these mutations might affect motor domain function a nd to attempt to correlate these effects with the mutant phenotype.