reproductive system
N |
• females produce normal litter sizes when mated to wild-type or heterozygous males
• males show no differences in testis histology, epididymal sperm count or sperm morphology relative to wild-type males
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• co-immunoprecipitation with anti-CATSPER1 antibody showed that, unlike all the other CatSper subunits examined, the protein level of CATSPER4 in the CatSper complex is significantly reduced in solubilized testis microsomes
• however, testicular levels of CATSPER1 and CATSPERB are normal in testis microsomes
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• CatSper components fail to exit the cell body and be targeted to the spermatid flagella; at step 10-12 of developing spermatids, CATSPER1 signal is only present in the cell body, unlike in wild-type spermatids where CATSPER1 is found in both the cell body and the prospective principal piece of the sperm flagellum
• assembly of CATSPER4 into the CatSper complex is reduced but not completely abolished in spermatids; remaining CATSPER4-containing CatSper complex is still unable to leave the cell body to reach the sperm flagella
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• no litters are produced when males are mated to wild-type or heterozygous females
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• spermatozoa are unable to fertilize cumulus-oocyte complex (COC)-intact oocytes in vitro
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• cauda epididymal sperm exhibit absent or barely detectable protein levels of other CatSper subunits and completely lack ICatSper, the sperm-specific and pH-sensitive ion current mediated by the CatSper channel
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• under capacitating conditions, activated cauda epididymal sperm exhibit a circulating swim path whereas wild-type sperm swim relatively straight
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• CASA showed that progressive motility is dramatically decreased under capacitation conditions
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• CASA showed that total motility is dramatically decreased under capacitation conditions
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• flagellar waveform analysis showed that capacitated sperm fail to develop hyperactivation whereas wild-type sperm develop asymmetric beating with increased amplitude
• velocity of curvilinear (VCL), average path velocity (VAP), and straight-line velocity (VSL) are significantly reduced, consistent with defective hyperactivation
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cellular
• under capacitating conditions, activated cauda epididymal sperm exhibit a circulating swim path whereas wild-type sperm swim relatively straight
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• CASA showed that progressive motility is dramatically decreased under capacitation conditions
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• CASA showed that total motility is dramatically decreased under capacitation conditions
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• flagellar waveform analysis showed that capacitated sperm fail to develop hyperactivation whereas wild-type sperm develop asymmetric beating with increased amplitude
• velocity of curvilinear (VCL), average path velocity (VAP), and straight-line velocity (VSL) are significantly reduced, consistent with defective hyperactivation
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endocrine/exocrine glands
• co-immunoprecipitation with anti-CATSPER1 antibody showed that, unlike all the other CatSper subunits examined, the protein level of CATSPER4 in the CatSper complex is significantly reduced in solubilized testis microsomes
• however, testicular levels of CATSPER1 and CATSPERB are normal in testis microsomes
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