{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:44:11Z","timestamp":1789195451694,"version":"build-2803163510"},"reference-count":33,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:p>Nuclear lamins are structural protein components of the nuclear envelope. Mutations in LMNA, the gene coding for A-type lamins, result in several human hereditary diseases, the laminopathies, which include Emery-Dreifuss muscular dystrophy, dilated cardiomyopathy, familial partial lipodystrophy and Hutchinson-Gilford progeria. Similar to the human conditions, it has been shown that Lmna\u2013\/\u2013 mice develop severe dystrophies of muscle and fat tissues. Here we report that Lmna\u2013\/\u2013 mice display impaired spermatogenesis, with a significant accumulation of spermatocytes I during early prophase I stages, while pachytene spermatocytes are severely defective in synaptic pairing of the sex chromosomes in particular, leading to massive apoptosis during the pachytene stage of meiosis I. In contrast, oogenesis remains largely unaffected in Lmna\u2013\/\u2013 mice. These results reveal A-type lamins as important determinants of male fertility.<\/jats:p>","DOI":"10.1242\/jcs.00975","type":"journal-article","created":{"date-parts":[[2004,3,2]],"date-time":"2004-03-02T19:38:32Z","timestamp":1078256312000},"page":"1173-1178","source":"Crossref","is-referenced-by-count":51,"title":["Disruption of spermatogenesis in mice lacking A-type lamins"],"prefix":"10.1242","volume":"117","author":[{"given":"Manfred","family":"Alsheimer","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Biocenter, University of Wu\u0308rzburg, Am Hubland, 97074 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodo","family":"Liebe","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Sewell","sequence":"additional","affiliation":[{"name":"Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702-1201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin L.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, MD 21702-1201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Scherthan","sequence":"additional","affiliation":[{"name":"Max-Planck-Institute for Molecular Genetics, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Benavente","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Biocenter, University of Wu\u0308rzburg, Am Hubland, 97074 Wu\u0308rzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042518535428500_REF1","doi-asserted-by":"crossref","unstructured":"Alsheimer, M. and Benavente, R. (1996). Change of karyoskeleton during mammalian spermatogenesis: expression pattern of nuclear lamin C2 and its regulation. Exp. Cell Res.228, 181-188.","DOI":"10.1006\/excr.1996.0315"},{"key":"2021042518535428500_REF2","doi-asserted-by":"crossref","unstructured":"Alsheimer, M., von Glasenapp, E., Hock, R. and Benavente, R. (1999). Architecture of the nuclear periphery of rat pachytene spermatocytes: distribution of nuclear envelope proteins in relation to synaptonemal complex attachment sites. Mol. Biol. Cell10, 1235-1245.","DOI":"10.1091\/mbc.10.4.1235"},{"key":"2021042518535428500_REF3","doi-asserted-by":"crossref","unstructured":"Benavente, R., Alsheimer, M. and von Glasenapp, E. (2004). The nuclear envelope at the attachment sites of mammalian meiotic telomeres. Chromosomes Today14, in press.","DOI":"10.1007\/978-94-017-1033-6_12"},{"key":"2021042518535428500_REF4","doi-asserted-by":"crossref","unstructured":"Bonne, G., Di Barletta, M. R., Varnous, S., Becane, H.M., Hammouda, E. H., Merlini, L., Muntoni, F., Greenberg, C. R., Gary F., Urtizberea, J. A. et al. (1999). Mutations in the gene encoding lamin A\/C cause autosomal dominant Emery-Dreifuss muscular distrophy. Nat. Genet.21, 285-288.","DOI":"10.1038\/6799"},{"key":"2021042518535428500_REF5","doi-asserted-by":"crossref","unstructured":"Burke, B. and Stewart, C. L. (2002). Life at the edge: the nuclear envelope and human disease. Nat. Rev. Mol. Cell. Biol.3, 575-585.","DOI":"10.1038\/nrm879"},{"key":"2021042518535428500_REF6","doi-asserted-by":"crossref","unstructured":"Cao, H. and Hegele, R. A. (2000). Nuclear lamin A\/C R428Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet.9, 109-112.","DOI":"10.1093\/hmg\/9.1.109"},{"key":"2021042518535428500_REF7","doi-asserted-by":"crossref","unstructured":"Cao, H. and Hegele, R. A. (2003). LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J. Hum. Genet.48, 271-274.","DOI":"10.1007\/s10038-003-0025-3"},{"key":"2021042518535428500_REF8","doi-asserted-by":"crossref","unstructured":"Cohen, M., Lee, K. K., Wilson, K. L. and Gruenbaum, Y. (2001). Transcriptional repression, apoptosis, human disease and the functional evolution of the nuclear lamina. Trends Biochem. Sci.26, 41-47.","DOI":"10.1016\/S0968-0004(00)01727-8"},{"key":"2021042518535428500_REF9","doi-asserted-by":"crossref","unstructured":"Collard, J. F., Senecal, J. L. and Raymond, Y. (1992). Redistribution of nuclear lamin A is an early event associated with differentiation of human promyelocytic leukemia HL-60 cells. J. Cell Sci.101, 657-670.","DOI":"10.1242\/jcs.101.3.657"},{"key":"2021042518535428500_REF10","doi-asserted-by":"crossref","unstructured":"De Sandre-Giovannoli, A. Chaouch, M., Kozlov S., Vallat, J. M., Tazir, M., Kassouri, N., Szepetowski, P., Hammadouche T., Vandenberghe, A., Stewart, C. L. et al. (2002). Homozygous defects in LMNA, encoding lamin A\/C nuclear envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am. J. Hum. Genet.70, 726-736.","DOI":"10.1086\/339274"},{"key":"2021042518535428500_REF11","doi-asserted-by":"crossref","unstructured":"Eriksson, M., Brown, W. T., Gordon, L. B., Glynn, M. W., Singer, J., Scott, L., Erdos, M. R., Robbins, C. M., Moses, T. Y., Berglund, P. et al. (2003). Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature423, 293-298.","DOI":"10.1038\/nature01629"},{"key":"2021042518535428500_REF12","doi-asserted-by":"crossref","unstructured":"Fatkin, D., MacRae, C., Sasaki T., Wolff, M. R., Porcu, M., Frenneaux, M., Atherton, J., Vidaillet, H. J., Jr, Spudich, S., De Girolami, U. et al. (1999). Missense mutations in the rod domain of the lamin A\/C gene as causes of dilated cardiomyopathy and conduction-system disease. New Engl. J. Med.341, 1715-1724.","DOI":"10.1056\/NEJM199912023412302"},{"key":"2021042518535428500_REF13","doi-asserted-by":"crossref","unstructured":"Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K. and Spann, T. P. (2002). Nuclear lamins: building blocks of nuclear architecture. Genes Dev.16, 533-547.","DOI":"10.1101\/gad.960502"},{"key":"2021042518535428500_REF14","doi-asserted-by":"crossref","unstructured":"Gruenbaum, Y., Wilson, K. L., Harel, A., Goldberg, M. and Cohen, M. (2000). Nuclear lamins: structural proteins with fundamental functions. J. Struct. Biol.129, 313-323.","DOI":"10.1006\/jsbi.2000.4216"},{"key":"2021042518535428500_REF15","doi-asserted-by":"crossref","unstructured":"Hunt, P. A. and Hassolt, T. J. (2002). Sex matters in meiosis. Science296, 2181-2183.","DOI":"10.1126\/science.1071907"},{"key":"2021042518535428500_REF16","doi-asserted-by":"crossref","unstructured":"Hutchison, C. J. (2002). Lamins: buildings blocks or regulators of gene expression? Nat. Rev. Mol. Cell. Biol.3, 847-858.","DOI":"10.1038\/nrm950"},{"key":"2021042518535428500_REF17","doi-asserted-by":"crossref","unstructured":"Lammers, J. H., Offenberg, H. H., van Aalderen, M., Vink, A. C., Dietrich, A. J. and Heyting, C. (1994). The gene encoding a major component of the lateral elements of synaptonemal complexes of the rat is related to X-linked lymphocyte-regulated genes. Mol. Cell. Biol.14, 1137-1146.","DOI":"10.1128\/MCB.14.2.1137"},{"key":"2021042518535428500_REF18","doi-asserted-by":"crossref","unstructured":"Li, B., Oestreich, S. and de Lange, T. (2000). Identification of human Rap1: implications for telomere evolution. Cell101, 471-483.","DOI":"10.1016\/S0092-8674(00)80858-2"},{"key":"2021042518535428500_REF19","doi-asserted-by":"crossref","unstructured":"Moens, P. B. (1995). Histones H1 and H4 of surface-spread meiotic chromosomes. Chromosoma104, 169-174.","DOI":"10.1007\/BF00352181"},{"key":"2021042518535428500_REF20","doi-asserted-by":"crossref","unstructured":"Odorisio, T., Rodriguez, T. A., Evans, E. P., Geiger, B. and Kepler, R. (1998). The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis. Nat. Genet.18, 257-261.","DOI":"10.1038\/ng0398-257"},{"key":"2021042518535428500_REF21","doi-asserted-by":"crossref","unstructured":"Oakberg, E. F. (1956). A description of spermatogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am. J. Anat.99, 391-413.","DOI":"10.1002\/aja.1000990303"},{"key":"2021042518535428500_REF22","doi-asserted-by":"crossref","unstructured":"Roeder, G. S. and Bailis, J. M. (2000). The pachytene checkpoint. Trends Genet.16, 395-403.","DOI":"10.1016\/S0168-9525(00)02080-1"},{"key":"2021042518535428500_REF23","unstructured":"Russell, L. D., Ettlin, R. A., Sinha Hikim, A. P. and Clegg, E. D. (1990).Histological and Histopathological Evaluation of the Testis. Clearwater: Cache River Press."},{"key":"2021042518535428500_REF24","doi-asserted-by":"crossref","unstructured":"Scherthan, H., Weich, S., Schwegler, H., Heyting, C., Ha\u0308rele, M. and Cremer, T. (1996). Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing. J. Cell Biol.134, 1109-1125.","DOI":"10.1083\/jcb.134.5.1109"},{"key":"2021042518535428500_REF25","doi-asserted-by":"crossref","unstructured":"Scherthan, H., Jerratsch, M., Dhar, S., Wang, Y. A., Goff, S. P. and Pandita, T. K. (2000a). Meiotic telomere distribution and Sertoli cell nuclear architecture are altered in Atm- and Atm-p53-deficient mice. Mol. Cell. Biol.20, 7773-7783.","DOI":"10.1128\/MCB.20.20.7773-7783.2000"},{"key":"2021042518535428500_REF26","doi-asserted-by":"crossref","unstructured":"Scherthan, H., Jerratsch, M., Li, B., Smith, S., Hulte\u0301n, M., Lock, T. and de Lange, T. (2000b). Mammalian meiotic telomeres: protein composition and redistribution in relation to nuclear pores. Mol. Biol. Cell11, 4189-4203.","DOI":"10.1091\/mbc.11.12.4189"},{"key":"2021042518535428500_REF27","doi-asserted-by":"crossref","unstructured":"Stewart, C. and Burke, B. (1987). Teratocarcinoma stem cells and early mouse embryos contain only a single major lamin polypeptide closely resembling lamin B. Cell51, 383-392.","DOI":"10.1016\/0092-8674(87)90634-9"},{"key":"2021042518535428500_REF28","doi-asserted-by":"crossref","unstructured":"Stuurman, N., Hein, S. and Aebi, U. (1998). Nuclear lamins: their structure, assembly, and interactions. J. Struct. Biol.122, 42-66.","DOI":"10.1006\/jsbi.1998.3987"},{"key":"2021042518535428500_REF29","doi-asserted-by":"crossref","unstructured":"Sullivan, T., Escalante-Alcalde, D., Bhatt, H., Anver, M., Bhat, N., Nagashima, K., Stewart, C. L. and Burke, B. (1999). Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol.147, 913-920.","DOI":"10.1083\/jcb.147.5.913"},{"key":"2021042518535428500_REF30","doi-asserted-by":"crossref","unstructured":"Vigouroux, C., Magre, J., Vantyghem, M. C., Bourut, C., Lascols, O., Shackleton, S., Lloyd, D. J., Guerci, B., Padova, G., Valensi, P. et al. (2000). Lamin A\/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes49, 1958-1962.","DOI":"10.2337\/diabetes.49.11.1958"},{"key":"2021042518535428500_REF31","doi-asserted-by":"crossref","unstructured":"Wilson, K. L., Zastrow, M. S. and Lee, K. K. (2001). Lamins and disease: insights into nuclear infrastructure. Cell104, 647-650.","DOI":"10.1016\/S0092-8674(02)01452-6"},{"key":"2021042518535428500_REF32","doi-asserted-by":"crossref","unstructured":"Yuan, L., Liu, J. G., Hoja, M. R., Wilbertz, J., Nordqvist, K. and Ho\u0308o\u0308g, C. (2002). Female germ cell aneupolidy and embryo death in mice lacking the meiosis-specific protein SCP3. Science296, 1115-1118.","DOI":"10.1126\/science.1070594"},{"key":"2021042518535428500_REF33","doi-asserted-by":"crossref","unstructured":"Zhu, X. D., Kuster, B., Mann, M., Petrini, J. H. and de Lange, T. (2000). Cell-cycle-regulated association of RAD50\/MRE\/11\/NBS1 with TRF2 and human telomeres. Nat. Genet.25, 347-352.","DOI":"10.1038\/77139"}],"container-title":["Journal of Cell Science"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/117\/7\/1173\/1529496\/1173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jcs\/article-pdf\/117\/7\/1173\/1529496\/1173.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:12:14Z","timestamp":1623715934000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jcs\/article\/117\/7\/1173\/28228\/Disruption-of-spermatogenesis-in-mice-lacking-A"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,3,1]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2004,3,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jcs.00975","relation":{},"ISSN":["1477-9137","0021-9533"],"issn-type":[{"value":"1477-9137","type":"electronic"},{"value":"0021-9533","type":"print"}],"subject":[],"published":{"date-parts":[[2004,3,1]]}}}