title: Molecular definition of an allelic series of mutations disrupting the mouse Lmx1a (dreher) gene.
abstract: Mice homozygous for the dreher (dr) mutation are characterized by pigmentation and skeletal abnormalities and striking behavioral phenotypes, including ataxia, vestibular deficits, and hyperactivity. The ataxia is associated with a cerebellar malformation that is remarkably similar to human Dandy-Walker malformation. Previously, positional cloning identified mutations in LIM homeobox transcription factor 1 alpha gene (Lmx1a) in three dr alleles. Two of these alleles, however, are extinct and unavailable for further analysis. In this article we report a new spontaneous dr allele and describe the Lmx1a mutations in this and six additional dr alleles. Strikingly, deletion null, missense, and frameshift mutations in these alleles all cause similar cerebellar malformations, suggesting that all dr mutations analyzed to date are null alleles.
authors.affiliation: Department of Human Genetics, University of Chicago, 920 E. 58th Street, CLSC 319, Chicago, Illinois, 60637, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Chizhikov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Steshina
authors.forename: Richard
authors.initials: R
authors.lastname: Roberts
authors.forename: Yesim
authors.initials: Y
authors.lastname: Ilkin
authors.forename: Linda
authors.initials: L
authors.lastname: Washburn
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Millen
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D002531:Cerebellum / Q000002:abnormalities / Q000166:cytology; D004252:DNA Mutational Analysis / Q000379:methods*; D003616:Dandy-Walker Syndrome / Q000235:genetics; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics*; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors
chemical_list: D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; C489692:Lmx1a protein, mouse; D014157:Transcription Factors