All Phenotypes Rfx2<tm1Hncs> MGI Mouse

premature death ( J:230575 )

• mice exhibiting severe growth retardation die before 2 months of age

growth/size/body region phenotype ( J:230575 )

N	• surviving mice exhibit no disruption in left-right asymmetry

decreased body size ( J:230575 )

• at P10, P15 and P20, some mice show significantly smaller body size than wild-type control mice

• however, no differences in body size or weight are observed shortly after birth

postnatal growth retardation ( J:230575 )

• ~25% of mice show severe growth retardation with increasing age

• some of the surviving mice display slight growth retardation

• however, most surviving mice grow normally without any obvious external or anatomical abnormalities

reproductive system phenotype ( J:230575 )

N	• adult female mice with normal growth are fertile and exhibit normal ovarian histology

multinucleated giant male germ cells ( J:230575 )

• histological analysis of adult males showed multinucleate giant cells in testis sections and in epididymal tubules

increased male germ cell apoptosis ( J:230575 )

• TUNEL assays showed that the number of apoptotic cells is >2-fold higher at P21 and 8-fold higher than in wild-type controls at P28 when multinucleate giant cells are observed

small testis ( J:230575 )

• testes from adult males are on average 30% smaller by weight than those from wild-type males

• testes are of normal size until P21 but significantly smaller starting from P28

abnormal spermatogenesis ( J:230575 )

• at P21, spermatogenesis is delayed in some males, with fewer seminiferous tubules containing round spermatids; when present, round spermatids are significantly fewer in number than in wild-type controls

abnormal sperm axoneme morphology ( J:230575 )

• no typical flagellar microtubules are detected in adult testes

azoospermia ( J:230575 )

• adult epididymis is completely devoid of mature spermatozoa

abnormal acrosome morphology ( J:230575 )

• at stage IV, many spermatids exhibit large round acrosomes or acrosomic vesicles that are not flattened

• at stage V-VI, a few spermatids have developed small arc-shaped acrosomes as in wild-type controls, but most spermatids show irregular-shaped acrosomes

• by stage VII, spermatids show abnormal acrosomes of varying shapes and degenerate, whereas wild-type spermatids exhibit large arc-shaped acrosomes that cover the nuclei

abnormal spermatid morphology ( J:230575 )

• at P21, round spermatids are significantly fewer in number than in wild-type controls

• elongating spermatids are completely absent in P28 testes

• most round spermatids do not mature beyond step 7 of spermiogenesis

• at P24, AFAF and alpha-tubulin staining of testis sections showed that early step round spermatids have a normal round acrosomal vesicle (AFAF+), as in wild-type controls; however, flagellum assembly is blocked and only dot-like alpha-tubulin signal is observed

abnormal manchette morphology ( J:230575 )

• in adult testes, a degenerative manchette structure is detected in multinucleate giant cells detached from the tubule wall

arrest of spermatogenesis ( J:230575 )

• at P28, elongating spermatids are completely absent in testes, with numerous detached round spermatids found in nearly every seminiferous tubular lumen

• at P35, no mature spermatozoa are seen in testes and degenerating multinucleate giant cells with dark staining nuclei are frequently detected

• however, the mitotic and meiotic phases of spermatogenesis are normal

• when wild-type spermatogonia are transplanted into seminiferous tubules of busulfan-pretreated males, spermatogenesis is successfully reconstituted in a subset of recipient tubules indicating a germ cell autonomous defect

arrest of spermiogenesis ( J:230575 )

• spermiogenesis is completely arrested at an early round spermatid step and accompanied by increased germ cell apoptosis

• round spermatids do not generate flagella, fail to differentiate into elongated spermatids and become detached from the seminiferous epithelium either individually or in clusters as multinucleate giant cells

• formation of the sperm flagellum is blocked at its earliest stage

• when wild-type spermatogonia are transplanted into testes, the manchette and flagella of elongating spermatids are observed, similar to wild-type controls

abnormal epididymis morphology ( J:230575 )

• no mature spermatozoa are detected in epididymal tubules; instead, large numbers of degenerating round spermatids and multinucleate giant cells are observed

male infertility ( J:230575 )

• adult male mice with normal growth are sterile

• however, copulatory plugs are formed, indicating normal sexual behavior