Globozoospermia in mice lacking the casein kinase II alpha ' catalytic subunit

Protein kinase casein kinase II (Ck2) is a cyclic-AMP and calcium-independe nt serine-threonine kinase that is composed of two catalytic subunits (alph a and alpha') and two regulatory beta-subunits. Ck2 is not a casein kinase in vivo, but over 100 substrates are known(1). The highly conserved amino a cid sequences of its subunits(2, 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, transl ation and control of metabolism. The Ck2 alpha and Ck2 alpha' isoforms (pro ducts of the genes Csnk2a1 and Csnk2a2, respectively) are highly homologous , but the reason for their redundancy and evolutionary conservation is unkn own. We find here that Csnk2a2 is preferentially expressed in late stages o f spermatogenesis, and male mice in which Csnk2a2 has been disrupted are in fertile, with oligospermia and globozoospermia ('round-headed' spermatozoa) . This is the first demonstration of a unique role for a Ck2 isoform in dev elopment. The primary spermatogenic defect in Csnk2a2(-/-) testis is a spec ific abnormality of anterior head shaping of elongating spermatids; this is the first defined gene that regulates sperm head morphogenesis. As the ger m cells differentiate, they are capable of undergoing chromatin condensatio n, although many abnormal cells are deleted through apoptosis or Sertoli ce ll phagocytosis. The few that survive to populate the epididymis exhibit he ad abnormalities similar to those described in human globozoospermia, thus Csnk2a2 may be a candidate gene for these inherited syndromes.