All Phenotypes Kpna6<tm1Bdr> MGI Mouse

prenatal lethality, incomplete penetrance ( J:311959 )

• mice are born at lower than predicted Mendelian ratios (18.8% versus expected 25%)

decreased body weight ( J:311959 )

• at 16 weeks of age, males show a significant reduction in body weight that is comparable to that observed in Kpna6^{Gt(AJ0609)Wtsi} homozygous males

postnatal growth retardation ( J:311959 )

• male pups exhibit severe postnatal growth retardation and this growth defect persists until adulthood

decreased male germ cell number ( J:311959 )

• male germ cell number is reduced and mature spermatozoa are rarely found in the lumen of seminiferous tubules

multinucleated giant male germ cells ( J:311959 )

• multinucleated spermatid giant cells are frequently observed

increased male germ cell apoptosis ( J:311959 )

• loss of pachytene spermatocytes is accompanied by an increased number of TUNEL+ cells

abnormal seminiferous tubule morphology ( J:311959 )

• mature spermatozoa are rarely found in the lumen of seminiferous tubules

• H&E staining showed aberrant sperm orientation in the seminiferous tubules

abnormal seminiferous tubule epithelium morphology ( J:311959 )

• seminiferous tubular epithelium is disorganized

• sperm transport through the seminiferous epithelium is severely disturbed

abnormal Sertoli cell morphology ( J:311959 )

• vimentin-based filaments are no longer stretched across the Sertoli cell cytosol but appear to be retracted and wrapped around the cell nuclei, indicating a defect in vimentin distribution

• however, beta-III tubulin organization in Sertoli cells is normal

decreased Sertoli cell number ( J:311959 )

• at 12-18 weeks of age, number of Sertoli cells per tubule is significantly lower than in wild-type controls

• however, Sertoli cell numbers are normal at 4 weeks of age

ectopic Sertoli cells ( J:311959 )

• aberrant localization of Sertoli cell nuclei is frequently observed in the seminiferous tubules

• immunofluorescence showed a marked reduction of the androgen receptor (AR) in Sertoli cell nuclei

small seminiferous tubules ( J:311959 )

• seminiferous tubule diameter is significantly smaller than in wild-type controls or Kpna6^{Gt(AJ0609)Wtsi} homozygous males

small testis ( J:311959 )

• adult males show a marked reduction in testis size

• however, serum testosterone levels are normal

decreased testis weight ( J:311959 )

• at 8-10 weeks of age, testis weight to body-weight ratio is 40% lower than in wild-type males

abnormal Sertoli cell barrier function ( J:311959 )

• immunological blood-testis barrier (BTB) appears to be slightly impaired as antibodies against testicular antigens are occasionally present

• however, no major changes in BTB integrity are detected in a biotin diffusion assay

abnormal spermatogenesis ( J:311959 )

• onset of the first wave of spermatogenesis is significantly delayed, consistent with Sertoli cell dysfunction

oligozoospermia ( J:311959 )

• total cauda epididymal sperm count is only 1.4% of that in wild-type males

abnormal sperm head morphology ( J:311959 )

• nearly all of remaining sperm found in the epididymides show abnormal heads

abnormal spermatid morphology ( J:311959 )

• number of step 1-8 round spermatids is significantly decreased

• however, ratio of round spermatids to pachytene spermatocytes is normal

abnormal spermatocyte morphology ( J:311959 )

• number of preleptotene spermatocytes per tubule is slightly decreased

• number of leptotene/zygotene spermatocytes is markedly decreased in stages X-XI, with a further reduction in the number of stage I-VIII pachytene spermatocytes

• ratio of pachytene to leptotene spermatocytes is significantly decreased

abnormal spermiogenesis ( J:311959 )

• although spermatid elongation occurs normally in stage IX tubules, elongating spermatids show abnormal nuclear shaping in subsequent steps and mature step 15-16 sperm are absent

• defects in spermiogenesis include incomplete sperm maturation and a massive reduction in sperm number, accompanied by impaired histone-protamine exchange, differential localization of the transcriptional regulator BRWD1, and altered expression of RFX2 target genes

abnormal spermiation ( J:311959 )

• sperm retention is often observed in stage IX-XII seminiferous tubules

abnormal epididymis morphology ( J:311959 )

• sloughed immature germ cells and germ cell debris are commonly detected in the epididymal lumen

abnormal caput epididymis morphology ( J:311959 )

• very few spermatozoa are detected in the caput of epididymides

abnormal cauda epididymis morphology ( J:311959 )

• spermatozoa are hardly detectable in the caudal epididymides

male infertility ( J:311959 )

• male mice are sterile

• however, vaginal plugs are observed in paired females