All Phenotypes Rnf216<em1Lijd> MGI Mouse

reproductive system phenotype ( J:307636 )

N	• adult female mice are fertile and show normal ovary weight and uterus length and weight relative to wild-type females

decreased male germ cell number ( J:307636 )

• at 8 weeks of age, the number of germ cells per testicular cross section is significantly lower than in wild-type testes

• however, Sertoli cell numbers are normal

increased male germ cell apoptosis ( J:307636 )

• at 8 weeks of age, male germ cell (spermatocyte) apoptosis is significantly increased in the seminiferous tubules, as shown by a TUNEL assay

small seminiferous tubules ( J:307636 )

• at 8 weeks of age, the diameters of seminiferous tubules are significantly smaller than in wild-type testes

small testis ( J:307636 )

• at 8 weeks of age, testes are significantly smaller than in wild-type males

decreased testis weight ( J:307636 )

• at 8 weeks of age, average testis weights are significantly lower than in wild-type males

• however, body weights are normal

abnormal testis physiology ( J:307636 )

• adult testes show significantly increased protein levels of PRKACB (protein kinase, cAMP dependent, catalytic, beta) and elevated PKA activity

• PRKACB protein and PKA activity are also significantly increased at 9 dpp

abnormal spermatogenesis ( J:307636 )

• seminiferous tubules contain normal germ cell numbers at 9 dpp but significantly fewer germ cells than wild-type tubules at 12 and 15 dpp, suggesting that prophase of meiosis I is impaired

• at 8 weeks of age, PAS and hematoxylin staining showed many dead pachytene spermatocytes at stage IV, suggesting impaired spermatogenesis at stage IV and abnormal progression from the zygotene to pachytene stage

• a few spermatids are still identified in testes at 8 weeks of age

oligozoospermia ( J:307636 )

• at 8 weeks of age, cauda epididymal sperm count is severely reduced relative to that in wild-type males

abnormal spermatocyte morphology ( J:307636 )

• at 8 weeks of age, the proportion of zygotene spermatocytes is significantly increased, whereas proportion of pachytene spermatocytes is significantly reduced

• however, the number of diplotene spermatocytes is not significantly altered

arrest of male meiosis ( J:307636 )

• meiosis I prophase is defective; spermatocytes are incompletely arrested at the zygotene stage and undergo apoptosis at approximately the pachytene stage

• increased PKA activity may, at least partly, contribute to disrupted meiosis

abnormal cauda epididymis morphology ( J:307636 )

• at 8 weeks of age, almost no mature spermatozoa are found in the cauda epididymal lumens

male infertility ( J:307636 )

• adult male mice are completely infertile