Phenotypes for Plekha5 Ptpn11 MGI:7281502 MGI Mouse

abnormal spermatocyte morphology ( J:250152 )

• number of SYCP3+ spermatocytes is significantly increased at 1 week but significantly decreased at 3 weeks of age

abnormal spermatogonia morphology ( J:250152 )

• number of PLZF+ undifferentiated spermatogonial stem cells (SSCs) is normal at 1 week of age but significantly reduced at 2-, 3- and 4 weeks of age

• unlike in controls where Kit (a differentiated SSC marker ) is first expressed at ~P6 and reaches a high level at 2 weeks of age, strong Kit signals are noted at P3 and at 1 week but are degraded by 2 weeks, suggesting untimely and excessive SSC differentiation

• number of STRA8+ differentiated SSCs is significantly increased at 1 week but gradually reduced in the disrupted tubule starting at 3 weeks of age

• when wild-type SSCs are seeded on primary Sertoli cells isolated from 2-week-old mutant males, clone formation ability of SSCs is impaired

• adenovirus infection with a constitutively active Shp2 mutant rescues the capacity of wild-type SSCs to form clones

decreased male germ cell number ( J:250152 )

• testes show gradual loss of the germ cells resulting in Sertoli cell-only phenotype

• ~31% of seminiferous tubules have lost all of the germ cells by 16 weeks of age

azoospermia ( J:250152 )

• no mature sperm are found in the edidymides at 8 weeks of age

increased male germ cell apoptosis ( J:250152 )

• at 4 weeks of age, testes contain significantly more TUNEL+ apoptotic cells than control testes

• however, the number of WT1+ Sertoli cells is normal

abnormal seminiferous tubule epithelium morphology ( J:250152 )

• at 3 weeks of age, the number of cells in the seminiferous tubule epithelium is decreased and cells exhibit a disordered arrangement

abnormal Sertoli cell barrier morphology ( J:250152 )

• at 2 weeks of age, junction proteins critical for original BTB assembly, including GJA1 (connexin 43), CLDN11 (claudin 11) and F11R (aka JAMA), show aberrant localization and are dispersed over the seminiferous tubules, instead of being arranged in a regular cycle between the basal and adluminal compartments as in control tubules

• CLDN11 and GJA1 protein expression is significantly increased whereas F11R expression is significantly reduced

• when primary Sertoli cells from 2-wk-old males are cultured in vitro, transepithelial electrical resistance values of the Sertoli cell monolayer fail to increase with cell growth and, unlike in control cells, do not reach a peak level on day 3, indicating impaired cell junctions

• adenovirus infection with a constitutively active Shp2 mutant rescues the tight junction defects and restores electrical resistance peak level on day 3

small seminiferous tubules ( J:250152 )

• seminiferous tubules become significantly thinner by 16 weeks of age

seminiferous tubule degeneration ( J:250152 )

• at 4 weeks of age, 84% of seminiferous tubules appear damaged and show cell loss, vacuolization, a chaotic arrangement of germ cells, and absence of elongated sperm

• by 16 weeks of age, tubules are severely destroyed; ~31% of tubules have lost all of the germ cells, become significantly thinner and contain only Sertoli cells

increased Leydig cell number ( J:250152 )

• Leydig cell hyperplasia is observed by 16 weeks of age

decreased testis weight ( J:250152 )

• average weight of testes is significantly lower than in controls males at 2-, 3- and 4 weeks of age

• however, body weight is normal

abnormal Sertoli cell barrier function ( J:250152 )

• at 2 weeks of age, an in vivo biotin tracing assay showed that the tracer dye penetrates into the adluminal compartment in 77% of seminiferous tubules, suggesting increased BTB permeability

arrest of spermatogenesis ( J:250152 )

• the initial stage of spermatogenesis is blocked, and germ cells are depleted due to excessive spermatogonial stem cell (SSC) differentiation

male infertility ( J:250152 )

• when mated with wild-type females, adult male mice do not produce any progeny despite normal vaginal plug formation