Mutations of the mouse Twist and sy (Fibrillin 2) genes induced by chemical mutagenesis of ES cells

A prior phenotype-based screen of mice derived from ethylmethanesulfonate-m utagenized embryonic stem cells yielded two mouse limb defect mutants. Anim als heterozygous for the polydactyly ems (Pde) mutation display preaxial po lydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and some times 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 h undred basepairs of genomic DNA upstream of the coding region failed to rev eal a mutation, suggesting that the lesion may be in a regulatory element o f the gene. sne is a new fused phalanges (fp) allele of the shaker-with-syn dactylism deletion complex (sy), and we show that the genomic lesion is a s mall deletion removing an entire exon, coincident with the insertion of the 3' end of a LINE element belonging to the TF subfamily. (C) 2001 academic Press.