New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis

Norimitsu Inoue, Karl D. Hess, Randall W. Moreadith, Laura L. Richardson, Mary Ann Handel, Mark L. Watson, Andrew R. Zinn

Research output: Contribution to journalArticle

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Abstract

Mammalian spermatogenesis is a complex developmental process. The analysis of mouse mutations has provided insight into biochemical pathways required for completion of this process. We previously described the autosomal recessive mouse morc(TgN(Tyr)1Az) (microrchidia) mutation, a serendipitous transgenic insertional mutation which causes arrest of spermatogenesis prior to the pachytene stage of meiosis prophase I. We now report the molecular characterization of the morc locus and positional cloning of a gene disrupted by the morc(TgN(Tyr)1AZ) mutation. This gene, which we term Morc, encodes a 108 kDa protein expressed specifically in male germ cells. The transgene integrated within the first intron of Morc and was accompanied by an intragenic deletion of ~ 13 kb of genomic sequences, removing exons 2-4 and abrogating expression of the wild-type transcript. Analysis of the MORC protein sequence revealed putative nuclear localization signals, two predicted coiled-coil structural motifs and limited homology to GHL (GyraseB, Hsp90, MutL) ATPase. Epitope-tagged MORC protein expressed in COS7 cells localized to the nucleus. We also cloned the human MORC homolog and show that it too is testis-specific, but closely related human genes are transcribed in multiple somatic tissues. Homologous proteins are also present in zebrafish, nematodes, slime mold and plants. Thus, cloning of Morc defines a novel gene family whose members are likely to serve important biological functions in both meiotic and mitotic cells of multicellular organisms.

Original languageEnglish (US)
Pages (from-to)1201-1207
Number of pages7
JournalHuman Molecular Genetics
Volume8
Issue number7
DOIs
StatePublished - 1999

Fingerprint

Spermatogenesis
Nuclear Proteins
Mutation
Genes
Organism Cloning
Pachytene Stage
Meiotic Prophase I
Nuclear Localization Signals
Proteins
Protein Sequence Analysis
Meiosis
Zebrafish
Transgenes
Germ Cells
Introns
Adenosine Triphosphatases
Testis
Epitopes
Exons
Fungi

ASJC Scopus subject areas

  • Genetics

Cite this

Inoue, N., Hess, K. D., Moreadith, R. W., Richardson, L. L., Handel, M. A., Watson, M. L., & Zinn, A. R. (1999). New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis. Human Molecular Genetics, 8(7), 1201-1207. https://doi.org/10.1093/hmg/8.7.1201

New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis. / Inoue, Norimitsu; Hess, Karl D.; Moreadith, Randall W.; Richardson, Laura L.; Handel, Mary Ann; Watson, Mark L.; Zinn, Andrew R.

In: Human Molecular Genetics, Vol. 8, No. 7, 1999, p. 1201-1207.

Research output: Contribution to journalArticle

Inoue, N, Hess, KD, Moreadith, RW, Richardson, LL, Handel, MA, Watson, ML & Zinn, AR 1999, 'New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis', Human Molecular Genetics, vol. 8, no. 7, pp. 1201-1207. https://doi.org/10.1093/hmg/8.7.1201
Inoue N, Hess KD, Moreadith RW, Richardson LL, Handel MA, Watson ML et al. New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis. Human Molecular Genetics. 1999;8(7):1201-1207. https://doi.org/10.1093/hmg/8.7.1201
Inoue, Norimitsu ; Hess, Karl D. ; Moreadith, Randall W. ; Richardson, Laura L. ; Handel, Mary Ann ; Watson, Mark L. ; Zinn, Andrew R. / New gene family defined by MORC, a nuclear protein required for mouse spermatogenesis. In: Human Molecular Genetics. 1999 ; Vol. 8, No. 7. pp. 1201-1207.
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