Globozoospermia in mice lacking the casein kinase II α′ catalytic subunit
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 known 1 . The highly conserved amino acid sequen...
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Veröffentlicht in: | Nature genetics 1999-09, Vol.23 (1), p.118-121 |
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Sprache: | eng |
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Zusammenfassung: | 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 known
1
. The highly conserved amino acid 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, 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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ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/12729 |