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Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit

Nature Genetics volume 23, pages 118–121 (1999)Cite this article

Abstract

Protein kinase casein kinase II (Ck2) is a cyclic-AMP and calcium-independent serine-threonine kinase that is composed of two catalytic subunits (α and α′) and two regulatory β-subunits. Ck2 is not a casein kinase in vivo, but over 100 substrates are known1. The highly conserved amino acid sequences of its subunits2,3 and their broad expression suggest that Ck2 may have a fundamental role in cell function. Ck2 has been implicated in DNA replication, regulation of basal and inducible transcription, translation and control of metabolism. The Ck2α and Ck2α′ isoforms (products of the genes Csnk2a1 and Csnk2a2, respectively) are highly homologous, but the reason for their redundancy and evolutionary conservation is unknown. We find here that Csnk2a2 is preferentially expressed in late stages of spermatogenesis, and male mice in which Csnk2a2 has been disrupted are infertile, with oligospermia and globozoospermia ('round-headed' spermatozoa). This is the first demonstration of a unique role for a Ck2 isoform in development. The primary spermatogenic defect in Csnk2a2–/– testis is a specific abnormality of anterior head shaping of elongating spermatids; this is the first defined gene that regulates sperm head morphogenesis. As the germ cells differentiate, they are capable of undergoing chromatin condensation, although many abnormal cells are deleted through apoptosis or Sertoli cell phagocytosis. The few that survive to populate the epididymis exhibit head abnormalities similar to those described in human globozoospermia, thus Csnk2a2 may be a candidate gene for these inherited syndromes.

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Figure 1: Homologous recombination of the Csnk2a2 locus.
Figure 2: DNA content of germ cells in Csnk2a2–/– mice compared with wild-type mice during spermatogenesis.
Figure 3: Ultrastuctural analysis of sperm from wild-type and Csnk2a2–/– mice.
Figure 4: Expression pattern of Ck2 subunits in wild-type testis.

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Acknowledgements

We thank P. Leder and C.D. O'Hara for assistance with transfection of ES cells; D. Ladd for the blastocyst injections; N. Chester, D. Marshak, A.R. Means and R.E. Braun for providing antibodies; R. Oates for providing anonymous human spermatozoa samples; P. Burgoyne for helpful discussions of Y-specific genes and identification of potential Ck2 phosphorylation sites in SSTY proteins; and members of the Seldin laboratory for helpful discussions. This work was supported by the NCI.

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Authors and Affiliations

  1. Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, 02118, Massachusetts, USA

    Xin Xu & David C. Seldin

  2. Department of Biochemistry, Boston University School of Medicine, Boston, 02118, Massachusetts, USA

    Paul A. Toselli

  3. Department of Physiology, Southern Illinois University School of Medicine, Carbondale, 62901, Illinois, USA

    Lonnie D. Russell

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  1. Xin Xu
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Correspondence to David C. Seldin.

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Xu, X., Toselli, P., Russell, L. et al. Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit. Nat Genet 23, 118–121 (1999). https://doi.org/10.1038/12729

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