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Morgan, D; Turnpenny, L; Goodship, J; Dai, W; Majumder, K; Matthews, L; Gardner, A; Schuster, G; Vien, L; Harrison, W; Elder, F F; Penman-Splitt, M; Overbeek, P; Strachan, T
Nature genetics 20, Številka: 2Journal Article
Visceral left-right asymmetry occurs in all vertebrates, but the inversion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed. We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events, our YAC phenotype rescue studies indicate that the mutant phenotype results from the deletion. After extensively characterizing the 47-kb deleted region and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determined the full-length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like repeat sequences. Characterization of complementing and non-complementing YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of this novel gene, which we have named inversin (Invs).
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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