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Human Molecular Genetics, 1999, Vol. 8, No. 7 1201-1207
© 1999 Oxford University Press

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

Norimitsu Inoue1, Karl D. Hess2,a, Randall W. Moreadith3,b, Laura L. Richardson4, Mary Ann Handel4, Mark L. Watson1,c and Andrew R. Zinn1,3,c,d

1Eugene McDermott Center for Human Growth and Development, 2Department of Pathology and 3Department of Internal Medicine, University of Texas Southwestern Medical School, 6000 Harry Hines Boulevard, Dallas, TX 75235, USA and 4Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, TN 37996, USA

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 morcTgN(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 morcTgN(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.

a Present address: Ambion Inc., 2130 Woodward Street 200, Austin, TX 78744, USA

b Present address: ThromboGene Ltd, 13012 Morehead Drive, Chapel Hill, NC 27514, USA

c These authors contributed equally to this work

d To whom correspondence should be addressed at: Eugene McDermott Center for Human Growth and Development, UT Southwestern Medical School, 6000 Harry Hines Boulevard, Dallas, TX 75235, USA. Tel: +1 214 648 1615; Fax: +1 214 648 1666; Email: andrew{at}mcdermott.swmed.edu

DDBJ/EMBL/GenBank accession nos AF084945, AF084946.


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