Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly.

@article{citeulike:2948002, abstract = {Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia (PCD), polycystic kidney disease (PKD), Usher syndrome, nephronophthisis, Bardet-Biedl syndrome (BBS), Alstrom syndrome and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are best known for leading to retinal degeneration, but have also been associated with ciliary dysfunctions affecting other tissues. To further study the involvement of RPGR in ciliopathies, transgenic mouse lines overexpressing RPGR were generated. Animals carrying the transgene in varying copy number were investigated. We found that infertility due to aberrant spermatozoa correlated with increased copy numbers. In animals with moderately increased gene copies of Rpgr, structural disorganization in the flagellar midpiece, outer dense fibers, and fibrous sheath was apparent. In contrast, in animals with high copy numbers condensed sperm heads were present but the flagellum was absent in the vast majority of spermatozoa although early steps of flagellar biogenesis were observed. This complexity of defects in flagellar assembly suggests a role of RPGR in intraflagellar transport (IFT) processes.}, author = {Brunner, Sandra and Colman, Dvora and Travis, Alexander J J. and Luhmann, Ulrich F O F. and Shi, Wei and Feil, Silke and Imsand, Coni and Nelson, Jacquelyn and Grimm, Christian and R\"{u}licke, Thomas and Fundele, Reinald and Neidhardt, John and Berger, Wolfgang }, citeulike-article-id = {2948002}, doi = {10.1095/biolreprod.107.067454}, issn = {0006-3363}, journal = {Biology of reproduction}, keywords = {male-fertility, mir, rpgr, sperm}, month = {June}, posted-at = {2008-07-01 13:42:09}, priority = {2}, title = {Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly.}, url = {http://dx.doi.org/10.1095/biolreprod.107.067454}, year = {2008} }

TY - JOUR ID - citeulike:2948002 L3 - citeulike-article-id:2948002 TI - Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly. JF - Biology of reproduction SN - 0006-3363 N2 - Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia (PCD), polycystic kidney disease (PKD), Usher syndrome, nephronophthisis, Bardet-Biedl syndrome (BBS), Alstrom syndrome and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are best known for leading to retinal degeneration, but have also been associated with ciliary dysfunctions affecting other tissues. To further study the involvement of RPGR in ciliopathies, transgenic mouse lines overexpressing RPGR were generated. Animals carrying the transgene in varying copy number were investigated. We found that infertility due to aberrant spermatozoa correlated with increased copy numbers. In animals with moderately increased gene copies of Rpgr, structural disorganization in the flagellar midpiece, outer dense fibers, and fibrous sheath was apparent. In contrast, in animals with high copy numbers condensed sperm heads were present but the flagellum was absent in the vast majority of spermatozoa although early steps of flagellar biogenesis were observed. This complexity of defects in flagellar assembly suggests a role of RPGR in intraflagellar transport (IFT) processes. KW - male-fertility KW - mir KW - rpgr KW - sperm AU - Brunner, Sandra AU - Colman, Dvora AU - Travis, Alexander J AU - Luhmann, Ulrich F O AU - Shi, Wei AU - Feil, Silke AU - Imsand, Coni AU - Nelson, Jacquelyn AU - Grimm, Christian AU - Rülicke, Thomas AU - Fundele, Reinald AU - Neidhardt, John AU - Berger, Wolfgang PY - 2008/06/25/ UR - http://dx.doi.org/10.1095/biolreprod.107.067454 ER -