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Cloning of inv, a gene that controls left/right asymmetry and kidney development

Nature volume 395, pages 177–181 (1998)Cite this article

Abstract

Most vertebrate internal organs show a distinctive left/right asymmetry. The inv (inversion of embryonic turning) mutation in mice was created previously by random insertional mutagenesis1; it produces both a constant reversal of left/right polarity (situs inversus) and cyst formation in the kidneys2. Asymmetric expression patterns of the genes nodal and lefty are reversed in the inv mutant3,4,5,6, indicating that inv may act early in left/right determination. Here we identify a new gene located at the inv locus. The encoded protein contains 15 consecutive repeats of an Ank/Swi6 motif7,8 at its amino terminus. Expression of the gene is the highest in the kidneys and liver among adult tissues, and is seen in presomite-stage embryos. Analysis of the transgenic genome and the structure of the candidate gene indicate that the candidate gene is the only gene that is disrupted in inv mutants. Transgenic introduction of a minigene encoding the candidate protein restores normal left/right asymmetry and kidney development in the inv mutant, confirming the identity of the candidate gene.

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Figure 1: The inv transgenic integration site and FISH.
Figure 2: Genomic organization of the inv gene, cDNA clones and Southern hybridization.
Figure 3: Northern blot analysis of embryonic (a) and adult (b) tissues of the mouse using the candidate inv cDNA.
Figure 4: Transgenic rescue of inv/inv by introducing the candidate inv gene.
Figure 5: Deduced amino-acid sequence of the inv candidate gene.

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Acknowledgements

We thank A. Takao for encouragement and support; R. Kucherlapati, S. Somlo and S. Aizawa for suggestions; H. Lehrach for YAC clones; M. Ishibashi and M.Yokoyama for mouse husbandry and embryo preservation; S. Ohishi and K. Mochida for mouse genotyping and histological sections; the staff of the TWMC for supporting our projects; and J. Miyazaki for providing the pCAGGS vector.

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Authors and Affiliations

  1. Department of Medicine, Kidney Center, 8-1 Kawada-cho, Shinjuku-ku, 162-8600, Tokyo, Japan

    Toshio Mochizuki, Ken Tsuchiya & Hiroshi Nihei

  2. Department of Anatomy and Developmental Biology, Tokyo Women's Medical University, School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, 162-8600, Tokyo, Japan

    Takahiko Yokoyama

  3. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, 565, Osaka, Japan

    Yukio Saijoh & Hiroshi Hamada

  4. Crest, Japan Science and Technology Corporation, Tokyo, 170-0013, Japan

    Yukio Saijoh, Hiroshi Hamada & Takahiko Yokoyama

  5. Mammalian Development Laboratory, National Institute of Genetics, 1111 Yata, Mishima-shi, 411, Japan

    Yasuaki Shirayoshi & Norio Nakatsuji

  6. Department of Genetics, Research Institute, International Medical Center of Japan, 1-21-1 Toyoma, Shinjuku-ku, 162, Tokyo, Japan

    Setsuo Takai & Kiyomi Yamada

  7. Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, 113, Tokyo, Japan

    Choji Taya & Hiromichi Yonekawa

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  1. Toshio Mochizuki
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  2. Yukio Saijoh
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  13. Takahiko Yokoyama
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Correspondence to Takahiko Yokoyama.

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Mochizuki, T., Saijoh, Y., Tsuchiya, K. et al. Cloning of inv, a gene that controls left/right asymmetry and kidney development. Nature 395, 177–181 (1998). https://doi.org/10.1038/26006

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