Affected homologous chromosome pairing and phosphorylation of testis specific histone, H2AX, in male meiosis under FKBP6 deficiency.
A gene for FK506 binding protein 6 (Fkbp6) expresses during a specific stage of male and female meiosis. Disruption of the gene influences male reproduction, i.e. arrests spermatogenesis, but not female reproduction. Using the mouse model (targeted disruption), the role of the gene in homologous chromosome pairing has been demonstrated in a previous study. For further understanding the function of Fkbp6 in chromosome synapsis, we evaluated chromosome pairings during male meiosis in the as/as rat, a spontaneous null mutation, and compared them with those of the mouse model. Electron microscopy of the pachytene nuclei unveiled several types of abnormal chromosome pairing in the rat model, as shown in the mouse previously. The frequencies of aberrant pairings in the knockout mice and mutant rats were 42 of 67 nuclei (62.7%) and 20 out of 74 nuclei (27.0%), respectively. In order to clarify the mechanism of male specific infertility in Fkbp6 deficiency, the localization of gammaH2AX, a marker protein of XY chromosome inactivation during male meiosis, was examined. Immunostaining of gammaH2AX unveiled normal localization of the molecule to XY chromosomes (XY body) in both models, showing the independency of FKBP6 in sex chromosome inactivation. Besides the XY body, focal localization of gammaH2AX was observed in accordance with the unsynapsed chromosomes in both types of null animal. These results indicate the fundamental role of Fkbp6 in homologous chromosome synapsis during male meiosis. In conclusion, male specific infertility under Fkbp6 deficiency remains unsolved.
Noguchi
Junko
J
Reproductive Biology Research Unit, National Institute of Agrobiological Sciences, Tsukuba, Japan. jgucci@nias.affrc.go.jp
Ozawa
Manabu
M
Nakai
Michiko
M
Somfai
Tamás
T
Kikuchi
Kazuhiro
K
Kaneko
Hiroyuki
H
Kunieda
Tetsuo
T
D000818:Animals; D015415:Biomarkers; D023902:Chromosome Pairing / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D051381:Rats; D011922:Rats, Mutant Strains; D012730:Sex Chromosomes / Q000502:physiology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D013737:Testis / Q000502:physiology*
D015415:Biomarkers; D006657:Histones; D022021:Tacrolimus Binding Proteins; C531061:FKBP6 protein, mouse; C531062:FKBP6 protein, rat; C475961:gamma-H2AX protein, mouse