Expression of transgenic PPP1CC2 in the testis of Ppp1cc-null mice rescues spermatid viability and spermiation but does not restore normal sperm tail ultrastructure, sperm motility, or fertility.
Two isoforms of phosphoprotein phosphatase 1, PPP1CC1 and PPP1CC2, are translated from alternatively spliced transcripts of a single gene, Ppp1cc, and differ only at their extreme C-termini. While PPP1CC1 expression is almost ubiquitous, PPP1CC2 is largely restricted to testicular germ cells and mature spermatozoa. Targeted deletion of Ppp1cc leads to sterility of -/- males due to a combination of gross structural defects in developing spermatids resulting in apoptosis and faulty spermiation. Because PPP1CC2 is the only PP1 isoform that demonstrates high-level expression in wild-type meiotic and postmeiotic male germ cells, we have tested whether its loss in Ppp1cc-/- males is largely responsible for manifestation of this phenotype by expressing PPP1CC2 transgenically in the testis of Ppp1cc-/- mice (rescue mice). Herein, we demonstrate that PPP1CC2 expression in the Ppp1cc-/- testis is antiapoptotic, thus reestablishing spermatid development and spermiation. However, because aberrant flagellar morphogenesis is incompletely ameliorated, rescue males remain infertile. Because these results suggest that expression of PPP1CC2 in developing germ cells is essential but insufficient for normal spermatogenesis to occur, appropriate spatial and temporal expression of both PPP1CC isoforms in the testis during spermatogenesis appears to be necessary to produce structurally normal fertility-competent spermatozoa.
Biological Sciences, Kent State University, Kent, Ohio, USA.
David C
DC
Soler
Suraj
S
Kadunganattil
Shandilya
S
Ramdas
Kimberly
K
Myers
Joaquim
J
Roca
Theresa
T
Slaughter
Stephen H
SH
Pilder
Srinivasan
S
Vijayaraghavan
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival; D010064:Embryo Implantation; D004822:Epididymis / Q000648:ultrastructure; D005260:Female; D005298:Fertility / Q000235:genetics*; D015870:Gene Expression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013077:Sperm Head / Q000648:ultrastructure; D013081:Sperm Motility / Q000235:genetics; D013082:Sperm Tail / Q000378:metabolism / Q000648:ultrastructure; D013087:Spermatids / Q000502:physiology; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000502:physiology*; D013737:Testis / Q000378:metabolism* / Q000648:ultrastructure; D019076:Transgenes
D020033:Protein Isoforms; D012333:RNA, Messenger; C517104:Ppp1cc protein, rat; D054645:Protein Phosphatase 1