Interallelic complementation at the mouse Mitf locus.
Mutations at the mouse microphthalmia locus (Mitf) affect the development of different cell types, including melanocytes, retinal pigment epithelial cells of the eye, and osteoclasts. The MITF protein is a member of the MYC supergene family of basic-helix-loop-helix-leucine-zipper (bHLHZip) transcription factors and is known to regulate the expression of cell-specific target genes by binding DNA as homodimer or as heterodimer with related proteins. The many mutations isolated at the locus have different effects on the phenotype and can be arranged in an allelic series in which the phenotypes range from near normal to white microphthalmic animals with osteopetrosis. Previous investigations have shown that certain combinations of Mitf alleles complement each other, resulting in a phenotype more normal than that of each homozygote alone. Here we analyze this interallelic complementation in detail and show that it is limited to one particular allele, Mitf(Mi-white) (Mitf(Mi-wh)), a mutation affecting the DNA-binding domain. Both loss- and gain-of-function mutations are complemented, as are other Mitf mutations affecting the DNA-binding domain. Furthermore, this behavior is not restricted to particular cell types: Both eye development and coat color phenotypes are complemented. Our analysis suggests that Mitf(Mi-wh)-associated interallelic complementation is due to the unique biochemical nature of this mutation.
Steingrímsson
Eiríkur
E
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland. eirikurs@hi.is
Arnheiter
Heinz
H
Hallsson
Jón Hallsteinn
JH
Lamoreux
M Lynn
ML
Copeland
Neal G
NG
Jenkins
Nancy A
NA
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005124:Eye Abnormalities; D005816:Genetic Complementation Test; D006579:Heterozygote; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors