LAUSR

Abstract Four isoforms of serine/threonine phosphatase type I, PP1&agr;, PP1&bgr;, PP1&ggr;1, and PP1&ggr;2, are derived from three genes. The PP1&ggr;1 and PP1&ggr;2 isoforms are alternately spliced transcripts of the protein phosphatase 1 catalytic subunit gamma gene (Ppp1cc). While PP1&ggr;1 is ubiquitous in somatic cells, PP1&ggr;2 is expressed exclusively in testicular germ cells and sperm. Ppp1cc knockout male mice (‐/‐), lacking both PP1&ggr;1 and PP1&ggr;2, are sterile due to impaired sperm morphogenesis. Fertility and normal sperm function can be restored by transgenic expression of PP1&ggr;2 alone in testis of Ppp1cc (‐/‐) mice. The purpose of this study was to determine whether the PP1&ggr;1 isoform is functionally equivalent to PP1&ggr;2 in supporting spermatogenesis and male fertility. Significant levels of transgenic PP1&ggr;1 expression occurred only when the transgene lacked a 1‐kb 3′UTR region immediately following the stop codon of the PP1&ggr;1 transcript. PP1&ggr;1 was also incorporated into sperm at levels comparable to PP1&ggr;2 in sperm from wild‐type mice. Spermatogenesis was restored in mice expressing PP1&ggr;1 in the absence of PP1&ggr;2. However, males from the transgenic rescue lines were subfertile. Sperm from the PP1&ggr;1 rescue mice were unable to fertilize eggs in vitro. Intrasperm localization of PP1&ggr;1 and the association of the protein regulators of the phosphatase were altered in epididymal sperm in transgenic PP1&ggr;1 compared to PP1&ggr;2. Thus, the ubiquitous isoform PP1&ggr;1, not normally expressed in differentiating germ cells, could replace PP1&ggr;2 to support spermatogenesis and spermiation. However, PP1&ggr;2, which is the PP1 isoform in mammalian sperm, has an isoform‐specific role in supporting normal sperm function and fertility.