Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal sheet formation and female fertility.
Peptidylarginine deiminase 6 (PAD6) is an enzyme that is uniquely expressed in male and female germ cells. To study the function of this enzyme in vivo we generated mice deficient for PAD6. Here we show that inactivation of the PAD6 gene in mice leads to female infertility whereas male fertility is not affected. The absence of the PAD6 protein and consequently absence of citrullination activity in oocytes results in dispersal of the cytoskeletal sheets in oocytes, indicating an essential role of these germ cell-specific structures in zygote/embryo development. PAD6 deficient mice do not show any other overt phenotype. Thus, we identify citrullination as a new regulator of fertility.
Esposito
G
G
Department of Target Discovery, NV Organon, 5340 BH Oss, The Netherlands.
Vitale
A M
AM
Leijten
F P J
FP
Strik
A M
AM
Koonen-Reemst
A M C B
AM
Yurttas
P
P
Robben
T J A A
TJ
Coonrod
S
S
Gossen
J A
JA
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002956:Citrulline / Q000378:metabolism; D003599:Cytoskeleton / Q000201:enzymology* / Q000378:metabolism* / Q000648:ultrastructure; D004622:Embryo, Mammalian / Q000166:cytology; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D005298:Fertility / Q000502:physiology*; D018390:Gene Targeting; D006867:Hydrolases / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology* / Q000648:ultrastructure; D010053:Ovary / Q000166:cytology / Q000254:growth & development; D000080065:Protein-Arginine Deiminase Type 6; D000076342:Protein-Arginine Deiminases; D012867:Skin / Q000166:cytology
D002956:Citrulline; D006867:Hydrolases; D000080065:Protein-Arginine Deiminase Type 6; D000076342:Protein-Arginine Deiminases; C523190:PADI6 protein, mouse