title: Mutations of the mouse Twist and sy (fibrillin 2) genes induced by chemical mutagenesis of ES cells.
abstract: A prior phenotype-based screen of mice derived from ethylmethanesulfonate-mutagenized embryonic stem cells yielded two mouse limb defect mutants. Animals heterozygous for the polydactyly ems (Pde) mutation display preaxial polydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and sometimes forelimbs. We now report that Pde is a new allele of the basic helix-loop-helix protein gene Twist. Sequencing the full-length cDNA and several hundred basepairs of genomic DNA upstream of the coding region failed to reveal a mutation, suggesting that the lesion may be in a regulatory element of the gene. sne is a new fused phalanges (fp) allele of the shaker-with-syndactylism deletion complex (sy), and we show that the genomic lesion is a small deletion removing an entire exon, coincident with the insertion of the 3' end of a LINE element belonging to the TF subfamily.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
authors.forename: V L
authors.initials: VL
authors.lastname: Browning
authors.forename: S S
authors.initials: SS
authors.lastname: Chaudhry
authors.forename: A
authors.initials: A
authors.lastname: Planchart
authors.forename: M J
authors.initials: MJ
authors.lastname: Dixon
authors.forename: J C
authors.initials: JC
authors.lastname: Schimenti
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005020:Ethyl Methanesulfonate / Q000494:pharmacology*; D005091:Exons / Q000235:genetics; D000071840:Fibrillin-2; D000071837:Fibrillins; D005804:Genes, Lethal / Q000235:genetics; D005816:Genetic Complementation Test; D005838:Genotype; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000187:drug effects* / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D020161:Physical Chromosome Mapping; D017689:Polydactyly / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013576:Syndactyly / Q000235:genetics; D014157:Transcription Factors; D051879:Twist-Related Protein 1
chemical_list: C000605728:Fbn2 protein, mouse; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D005020:Ethyl Methanesulfonate