title: Molecular basis of mouse microphthalmia (mi) mutations helps explain their developmental and phenotypic consequences.
abstract: Mutations in the mouse microphthalmia (mi) gene affect the development of a number of cell types including melanocytes, osteoclasts and mast cells. Recently, mutations in the human mi gene (MITF) were found in patients with Waardenburg Syndrome type 2 (WS2), a dominantly inherited syndrome associated with hearing loss and pigmentary disturbances. We have characterized the molecular defects associated with eight murine mi mutations, which vary in both their mode of inheritance and in the cell types they affect. These molecular data, combined with the extensive body of genetic data accumulated for murine mi, shed light on the phenotypic and developmental consequences of mi mutations and offer a mouse model for WS2.
authors.affiliation: Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702.
authors.forename: E
authors.initials: E
authors.lastname: Steingrímsson
authors.forename: K J
authors.initials: KJ
authors.lastname: Moore
authors.forename: M L
authors.initials: ML
authors.lastname: Lamoreux
authors.forename: A R
authors.initials: AR
authors.lastname: Ferré-D'Amaré
authors.forename: S K
authors.initials: SK
authors.lastname: Burley
authors.forename: D C
authors.initials: DC
authors.lastname: Zimring
authors.forename: L C
authors.initials: LC
authors.lastname: Skow
authors.forename: C A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: H
authors.initials: H
authors.lastname: Arnheiter
authors.forename: N G
authors.initials: NG
authors.lastname: Copeland
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D003638:Deafness / Q000235:genetics; D004195:Disease Models, Animal; D005127:Eye Color / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005799:Genes, Dominant; D006200:Hair Color / Q000235:genetics; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D016350:Leucine Zippers; D008407:Mast Cells / Q000473:pathology; D008544:Melanocytes / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D051739:Microphthalmia-Associated Transcription Factor; D008850:Microphthalmos / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009432:Neural Crest / Q000473:pathology; D010022:Osteopetrosis / Q000235:genetics; D010641:Phenotype; D011487:Protein Conformation; D012326:RNA Splicing; D014071:Tooth Abnormalities / Q000235:genetics; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000145:classification / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D014157:Transcription Factors