Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis.
Meiosis is a critical stage of gametogenesis in which alignment and synapsis of chromosomal pairs occur, allowing for the recombination of maternal and paternal genomes. Here we show that FK506 binding protein (Fkbp6) localizes to meiotic chromosome cores and regions of homologous chromosome synapsis. Targeted inactivation of Fkbp6 in mice results in aspermic males and the absence of normal pachytene spermatocytes. Moreover, we identified the deletion of Fkbp6 exon 8 as the causative mutation in spontaneously male sterile as/as mutant rats. Loss of Fkbp6 results in abnormal pairing and misalignments between homologous chromosomes, nonhomologous partner switches, and autosynapsis of X chromosome cores in meiotic spermatocytes. Fertility and meiosis are normal in Fkbp6 mutant females. Thus, Fkbp6 is a component of the synaptonemal complex essential for sex-specific fertility and for the fidelity of homologous chromosome pairing in meiosis.
Crackower
Michael A
MA
Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), c/o Dr. Bohrgasse 7, 1030, Vienna, Austria.
Kolas
Nadine K
NK
Noguchi
Junko
J
Sarao
Renu
R
Kikuchi
Kazuhiro
K
Kaneko
Hiroyuki
H
Kobayashi
Eiji
E
Kawai
Yasuhiro
Y
Kozieradzki
Ivona
I
Landers
Rushin
R
Mo
Rong
R
Hui
Chi-Chung
CC
Nieves
Edward
E
Cohen
Paula E
PE
Osborne
Lucy R
LR
Wada
Teiji
T
Kunieda
Tetsuo
T
Moens
Peter B
PB
Penninger
Josef M
JM
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D023902:Chromosome Pairing / Q000502:physiology*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D005091:Exons; D005260:Female; D005298:Fertility / Q000502:physiology*; D018390:Gene Targeting; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008540:Meiosis; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009866:Oogenesis; D010053:Ovary / Q000502:physiology; D011418:Prophase; D051381:Rats; D017384:Sequence Deletion; D013087:Spermatids / Q000502:physiology; D013090:Spermatocytes / Q000502:physiology / Q000648:ultrastructure; D013091:Spermatogenesis; D013573:Synaptonemal Complex / Q000502:physiology*; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D013737:Testis / Q000502:physiology; D014960:X Chromosome / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C115725:FKBP6 protein, human; D009687:Nuclear Proteins; C489753:SYCP1 protein, human; C490060:SYCP3 protein, human; C489754:Sycp1 protein, mouse; C078744:Sycp1 protein, rat; C490062:Sycp3 protein, mouse; C085453:Sycp3 protein, rat; D022021:Tacrolimus Binding Proteins