Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis

Michael A. Crackower, Nadine K. Kolas, Junko Noguchi, Renu Sarao, Kazuhiro Kikuchi, Hiroyuki Kaneko, Eiji Kobayashi, Yasuhiro Kawai, Ivona Kozieradzki, Rushin Landers, Rong Mo, Chi Chung Hui, Edward Nieves, Paula E. Cohen, Lucy R. Osborne, Teiji Wada, Tetsuo Kunieda, Peter B. Moens, Josef M. Penninger

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Abstract

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 mates 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.

Original languageEnglish (US)
Pages (from-to)1291-1295
Number of pages5
JournalScience
Volume300
Issue number5623
DOIs
StatePublished - May 23 2003

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Crackower, M. A., Kolas, N. K., Noguchi, J., Sarao, R., Kikuchi, K., Kaneko, H., Kobayashi, E., Kawai, Y., Kozieradzki, I., Landers, R., Mo, R., Hui, C. C., Nieves, E., Cohen, P. E., Osborne, L. R., Wada, T., Kunieda, T., Moens, P. B., & Penninger, J. M. (2003). Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis. Science, 300(5623), 1291-1295. https://doi.org/10.1126/science.1083022