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

doi:10.1126/science.1083022

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

Biochemistry

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182 Scopus citations

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 language	English (US)
Pages (from-to)	1291-1295
Number of pages	5
Journal	Science
Volume	300
Issue number	5623
DOIs	https://doi.org/10.1126/science.1083022
State	Published - 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

Crackower, MA, Kolas, NK, Noguchi, J, Sarao, R, Kikuchi, K, Kaneko, H, Kobayashi, E, Kawai, Y, Kozieradzki, I, Landers, R, Mo, R, Hui, CC, Nieves, E, Cohen, PE, Osborne, LR, Wada, T, Kunieda, T, Moens, PB & Penninger, JM 2003, 'Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis', Science, vol. 300, no. 5623, pp. 1291-1295. https://doi.org/10.1126/science.1083022

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title = "Essential role of Fkbp6 in male fertility and homologous chromosome pairing in meiosis",

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.",

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

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AU - Crackower, Michael A.

AU - Kolas, Nadine K.

AU - Noguchi, Junko

AU - Sarao, Renu

AU - Kikuchi, Kazuhiro

AU - Kaneko, Hiroyuki

AU - Kobayashi, Eiji

AU - Kawai, Yasuhiro

AU - Kozieradzki, Ivona

AU - Landers, Rushin

AU - Mo, Rong

AU - Hui, Chi Chung

AU - Nieves, Edward

AU - Cohen, Paula E.

AU - Osborne, Lucy R.

AU - Wada, Teiji

AU - Kunieda, Tetsuo

AU - Moens, Peter B.

AU - Penninger, Josef M.

PY - 2003/5/23

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N2 - 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.

AB - 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.

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

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