S. Mazeyrat et al., A Y-encoded subunit of the translation initiation factor Eif2 is essentialfor mouse spermatogenesis, NAT GENET, 29(1), 2001, pp. 49-53
In mouse and man, deletions of specific regions of the Y chromosome have be
en linked to early failure of spermatogenesis and consequent sterility; the
Y chromosomal gene(s) with this essential early role in spermatogenesis ha
ve not been identified. The partial deletion of the mouse Y short arm (the
Sxr(b) deletion) that occurred when Tp(Y)1Ct(Sxr-b) (hereafter Sxr(b)) aros
e from Tp(Y)1CT(Sxr-b) (hereafter Sxr(a)) defines Spy, a Y chromosomal fact
or essential for normal spermatogonial proliferation(1-3). Molecular analys
is has identified six genes that lie within the deletion: Ube1y1 (refs. 4,5
), Smcy(6), Uty(7), Usp9y (also known as Dffry)(8), Eif2s3y (also known as
Eif-2 gammaY)(9) and Dby(10); all have closely similar X-encoded homologs.
of the Y-encoded genes, Ube1y1 and Dby have been considered strong candidat
es for mouse Spy function(4,5,10,11), whereas Smcy has been effectively rul
ed out as a candidate(12). There is no Ube1y1 homolog in man, and DBY, eith
er alone or in conjunction with USP9Y, is the favored candidate for an earl
y spermatogenic role(10,13-15). Here we show that introduction of Ube1y1 an
d Dby as transgenes. into Sxr(b)-deletion mice fails to overcome the sperma
togenic block. However, the introduction of Eif2s3y restores normal spermat
ogonial proliferation and progression through meiotic prophase. Therefore,
Eif2s3y, which encodes a subunit of the eukaryotic translation initiation f
actor Eif2, is Spy.