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Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse

Nature Genetics volume 20, pages 149–156 (1998)Cite this article

An Erratum to this article was published on 01 November 1998

Abstract

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 reversed1. We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events1,2, 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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Figure 1: Genomic organization of the mouse Invs gene and cDNA contig assembly.
Figure 2: Phenotype rescue.
Figure 3: Chromosome FISH.
Figure 4: Expression of the novel gene containing ankyrin-like repeats.
Figure 5: cDNA sequence of Invs.
Figure 6: Inferred Invs protein sequence and tandum ankyrin-like repeats.
Figure 7: Analysis of genomic organization and expression of Invs in YAC transgenic lines.

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Acknowledgements

We thank M. Weddle and J. Ellsworth for help in preparing the manuscript; J. Ash and J. Reddan for help designing and assembling the figures; B. Harris for technical assistance; S. Dunwoodie and R. Beddington for providing E7.5 cDNA filters; T. Yokoyama for the G16 and E121 cosmid clones; and M. Finegold for helpful discussions regarding the kidney and pancreatic pathology. All animal experiments were done in accordance with NIH guidelines. This work was financially supported by the University of Newcastle upon Tyne Research Committee, the British Heart Foundation, the Wellcome Trust, the UK Medical Research Council and the US N.I.H.

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  1. David Morgan, Lee Turnpenny, Judith Goodship, Miranda Penman-Splitt and Tom Strachan: Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU,UK . *These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, NE1 7RU, UK

    David Morgan *, Lee Turnpenny *, Judith Goodship, Miranda Penman-Splitt & Tom Strachan

  2. Departments of Cell Biology and Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, USA

    Weilie Dai, Kumud Majumder, Gaby Schuster, Long Vien & Paul Overbeek

  3. The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, CB10 1RQ, Cambridge, UK

    Lucy Matthews & Alison Gardner

  4. Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center, Houston, 77030, Texas, USA

    Wilbur Harrison & Frederick F.B. Elder

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Correspondence to Judith Goodship or Tom Strachan.

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Morgan, D., Turnpenny, L., Goodship, J. et al. Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse. Nat Genet 20, 149–156 (1998). https://doi.org/10.1038/2450

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