All Phenotypes Orai1<Gt(XL922)Byg> MGI Mouse

• mature adult males show a significant reduction in total body weight relative to wild-type and heterozygous controls

reproductive system phenotype ( J:315408 )

N	• female mice are fully fertile

multinucleated giant male germ cells ( J:315408 )

• by 12-16 weeks of age, many seminiferous tubules contain multinucleated germ cells

decreased sperm progressive motility ( J:315408 )

• cauda epididymal sperm show a severe reduction in progressive motility

asthenozoospermia ( J:315408 )

• cauda epididymal sperm show severe defects in motility

abnormal male germ cell physiology ( J:315408 )

• dispersed testicular cells (most of which are haploid and thus presumably germ cells) exhibit complete loss of store-operated Ca²⁺ entry in response to the sarcoplasmic-endoplasmic reticulum Ca²⁺-ATPase inhibitor, thapsigargin

abnormal seminiferous tubule epithelium morphology ( J:315408 )

• adult 12- to 16-week-old males exhibit abnormalities in junctional complexes (Sertoli-Sertoli, Sertoli-spermatid, and spermatid-spermatid via desmosomes)

abnormal Sertoli cell barrier morphology ( J:315408 )

• adult 12- to 16-week-old males show swelling of the junctional complexes between Sertoli cells

abnormal Sertoli cell morphology ( J:315408 )

• some Sertoli cells exhibit a large, loosely-distended cytoplasm with swollen mitochondria, distended Golgi complexes and an increase in residual bodies, some containing small lipid droplets

abnormal ectoplasmic specialization morphology ( J:315408 )

• adult 12- to 16-week-old males show swelling of the junctional complexes between Sertoli cells and spermatids

dilated seminiferous tubule ( J:315408 )

• by 12-16 weeks of age, many seminiferous tubules are dilated

seminiferous tubule degeneration ( J:315408 )

• males exhibit progressive degeneration and atrophy of the seminiferous tubules

• by 12-16 weeks of age, many tubules are atrophic and contain multinucleated germ cells, sloughed germ cells, abnormal residual bodies and cellular debris

decreased testis weight ( J:315408 )

• mature adult males show a small but significant reduction in testis weight relative to wild-type and heterozygous controls

abnormal spermatogenesis ( J:315408 )

• although abnormalities are observed at several stages of spermatogenesis, a major defect is observed in mid- to late-stage elongating spermatid development

oligozoospermia ( J:315408 )

• total cauda epididymal sperm count is severely reduced

abnormal sperm head morphology ( J:315408 )

• when present, late elongating spermatids show extensive malformations of the sperm head

abnormal spermatid morphology ( J:315408 )

• spermatid maturation is disrupted at 8-10 weeks of age

• early elongating spermatids have an abnormal head and loosely stippled to granular nuclear material

• near complete loss of elongated spermatids is seen at 12-16 weeks of age

• when present, late elongating spermatids show extensive head malformations

abnormal spermatocyte morphology ( J:315408 )

• spermatocytes display granular, electron lucent nuclear chromatin

abnormal spermiogenesis ( J:315408 )

• at 8 and 10 weeks of age, spermatid maturation is disrupted; many stage VII seminiferous tubules exhibit degenerate, clumped and reduced numbers of elongated spermatids, and in some cases degeneration and loss of round spermatids

• earlier stage tubules (I, II/III, V, VI) show vacuolation, exfoliation of spermatocytes and round spermatids, and decreased elongated spermatid numbers

• stages IX and XII tubules display degeneration and a reduced number of elongated spermatids

• changes in seminiferous tubules are worse at 10 weeks and by 12-16 weeks many tubules are atrophic, dilated and contain multinucleated germ cells, sloughed germ cells, abnormal residual bodies and cellular debris

abnormal cauda epididymis morphology ( J:315408 )

• cauda epididymis contains very few sperm but many degenerate cells and cellular debris

male infertility ( J:315408 )

• mature adult (12- to 16- week-old) male mice failed to sire offspring in rotated matings with wild-type females

• however, vaginal plugs are observed in paired females