Abstract
Mutations of the mouse limb deformity locus, ld, map to Chromosome (Chr) 2 and result in defects in the morphogenesis and patterning of the limb and kidney. Complementation studies have defined the existence of five recessive ld alleles. Remarkably, two of these, ld TgHdand ld TgBri, are transgene-induced mutations. Recovery of the first transgene insertional allele, ld TgHd, facilitated the molecular cloning of a large (>200 kb) candidate gene at the ld locus. This gene is broadly transcribed and encodes a set of novel protein isoforms, termed formins. Here we present characterization of the ld TgBrimutation that supports the molecular identification of the ld gene. We show that the ld TgBrifails to complement both the ld TgHdand the ld ORalleles and that it has undergone a genomic deletion that disrupts the cloned ld gene and its transcripts. Curiously, the ld TgBrideletion encompasses the same 11-kb interval in which the ld TgHdinsertion occurred and in which a chromosomal rearrangement has been identified in a third allele, ld In2. These findings suggest that this region of the ld gene is a preferential site for illegitimate recombination.
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Vogt, T.F., Jackson-Grusby, L., Wynshaw-Boris, A.J. et al. The same genomic region is disrupted in two transgene-induced limb deformity alleles. Mammalian Genome 3, 431–437 (1992). https://doi.org/10.1007/BF00356152
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DOI: https://doi.org/10.1007/BF00356152