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A protein kinase encoded by the t complex responder gene causes non-mendelian inheritance

Nature volume 402, pages 141–146 (1999)Cite this article

Abstract

Males heterozygous for the t-haplotype form of mouse chromosome 17 preferentially transmit the t-chromosome to their progeny. Several distorter/sterility loci carried on the t-haplotype together impair flagellar function in all spermatozoa whereas the responder, Tcr, rescues t-sperm but not wild-type sperm. Thus, t-sperm have an advantage over wild-type sperm in fertilizing egg cells. We have isolated Tcr by positional cloning and show that it is a member of a novel protein kinase gene family, designated Smok, which is expressed late during spermiogenesis. Smok kinases are components of a signal cascade which may control sperm motility. Tcr has a reduced kinase activity, which may allow it to counterbalance a signalling impairment caused by the distorter/sterility loci. Tcr transgene constructs cause non-mendelian transmission of chromosomes on which they are carried, which leads to sex-ratio distortion when Tcr cosegregates with the Y chromosome.

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Figure 1: Positional cloning identifies Tcr as a member of a novel gene family.
Figure 2: Predicted protein sequences of Tcr and Smok family members.
Figure 3: Smok genes and Tcr are expressed during spermiogenesis.
Figure 4: Proposed mechanism producing TRD and male sterility.

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Acknowledgements

We thank M. F. Lyon, K. Artzt, J.-L. Guenet and J. Nadeau for mouse strains and DNA; A.-M. Frischauf for a cosmid library of the genotype tw12/tw12; B. Engist for technical assistance; S. Kuschert and H. Garbers for DNA injections; U. Stauffer for maintenance of strains; A. Bauer and M. Leitges for suggestions on kinase assays; D. Solter and R. Kemler for support; and S. Gasca, D. Solter, R. Cassada and M. Mallo for comments and suggestions on the manuscript.

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Author notes

  1. K. John McLaughlin

    Present address: Center for Animal Transgenesis and Germ Cell Research, The School of Veterinary Medicine, New Bolton Center, Myrin Building, 382 W. Street Rd, Kennett Square, Pennsylvania, 19348, USA

  2. Bernhard G. Herrmann: Correspondence and requests for materials should be addressed to B.G.H. Gene sequences have been submitted to the EMBL Nucleotide Sequence Database; accession numbers: Tcrt6, AJ245452; Smok2+Balb, AJ245453; Smok2tw5, AJ245454; Smoktw12, AJ245455; Smok+129, AJ245456.

Authors and Affiliations

  1. Max-Planck-Institute of Immunobiology, Stübeweg 51, Freiburg, 79108, Germany

    Bernhard G. Herrmann, Birgit Koschorz, Karin Wertz, K. John McLaughlin & Andreas Kispert

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Correspondence to Bernhard G. Herrmann.

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Herrmann, B., Koschorz, B., Wertz, K. et al. A protein kinase encoded by the t complex responder gene causes non-mendelian inheritance. Nature 402, 141–146 (1999). https://doi.org/10.1038/45970

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