Essential Role of Fkbp6 in Male Fertility and Homologous Chromosome Pairing in Meiosis

• Published in: Science (American Association for the Advancement of Science) Vol. 300; no. 5623; pp. 1291 - 1295
• Main Authors: Crackower, Michael A., Kolas, Nadine K., Noguchi, Junko, Sarao, Renu, Kikuchi, Kazuhiro, Kaneko, Hiroyuki, Kobayashi, Eiji, Kawai, Yasuhiro, Kozieradzki, Ivona, Landers, Rushin, Mo, Rong, Hui, Chi-Chung, Nieves, Edward, Cohen, Paula E., Osborne, Lucy R., Wada, Teiji, Kunieda, Tetsuo, Moens, Peter B., Penninger, Josef M.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 23.05.2003; The American Association for the Advancement of Science
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Biological and medical sciences; Carrier proteins; Cell Cycle Proteins; Cell division; Chromosome pairing; Chromosome Pairing - physiology; Chromosomes; Cloning, Molecular; Coding; Cores; DNA-Binding Proteins; Down Syndrome; Exons; Female; Female fertility; Females; Fertility; Fertility - physiology; Fidelity; Fundamental and applied biological sciences. Psychology; Gene Targeting; Genetic aspects; Genetics; House mouse; Humans; Inactivation; Infertility, Male - genetics; Infertility, Male - physiopathology; Male; Males; Meiosis; Men; Mice; Molecular and cellular biology; Molecular Sequence Data; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oogenesis; Ovary - physiology; Pachytene stage; Prophase; Proteins; Rats; Sequence Deletion; Sex chromosomes; Spermatids - physiology; Spermatocytes; Spermatocytes - physiology; Spermatocytes - ultrastructure; Spermatogenesis; Synaptonemal Complex - physiology; Tacrolimus Binding Proteins - chemistry; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - physiology; Testes; Testis - physiology; Transport proteins; X Chromosome - physiology; Genetics
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1083022

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.