title: Molecular genetic dissection of mouse unconventional myosin-VA: head region mutations.
abstract: The mouse dilute (d) locus encodes unconventional myosin-VA (MyoVA). Mice carrying null alleles of dilute have a lightened coat color and die from a neurological disorder resembling ataxia and opisthotonus within three weeks of birth. Immunological and ultrastructural studies suggest that MyoVA is involved in the transport of melanosomes in melanocytes and smooth endoplasmic reticulum in cerebellar Purkinje cells. In studies described here, we have used an RT-PCR-based sequencing approach to identify the mutations responsible for 17 viable dilute alleles that vary in their effects on coat color and the nervous system. Seven of these mutations mapped to the MyoVA motor domain and are reported here. Crystallographic modeling and mutant expression studies were used to predict how these mutations might affect motor domain function and to attempt to correlate these effects with the mutant phenotype.
authors.affiliation: ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Huang
authors.forename: M J
authors.initials: MJ
authors.lastname: Cope
authors.forename: V
authors.initials: V
authors.lastname: Mermall
authors.forename: M C
authors.initials: MC
authors.lastname: Strobel
authors.forename: J
authors.initials: J
authors.lastname: Kendrick-Jones
authors.forename: L B
authors.initials: LB
authors.lastname: Russell
authors.forename: M S
authors.initials: MS
authors.lastname: Mooseker
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
authors.forename: N A
authors.initials: NA
authors.lastname: Jenkins
mesh_terms: D000483:Alleles; D000818:Animals; D018360:Crystallography, X-Ray; D005260:Female; D015870:Gene Expression; D006200:Hair Color / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics*; D008297:Male; D051379:Mice; D008958:Models, Molecular; D016296:Mutagenesis; D018995:Myosin Heavy Chains; D024701:Myosin Type V
chemical_list: D007381:Intermediate Filament Proteins; C513082:Myo5a protein, mouse; D024701:Myosin Type V; D018995:Myosin Heavy Chains