Phenotypes associated with this allele

• Allele Symbol: Plekha5⁺
• Allele Name: wild type
• Allele ID: MGI:3051015
• Summary: 20 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: C57BL/6 * C57BL/6J * SJL	MGI:5446816
ht2	Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: C57BL/6 * SJL	MGI:4431085
cn3	Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.2Mbp Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129 * C57BL/6 * SJL	MGI:7327644
cn4	Gja1^tm1Kwi/Gja1^tm1Kwi Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4366524
cn5	Pex5^tm1Pec/Pex5^tm1Pec Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3851809
cn6	Ar^tm1Verh/Y Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6	MGI:3036125
cn7	Ptpn11^tm1Gsf/Ptpn11^tm1Gsf Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL	MGI:7281502
cn8	Tsc22d3^tm1.1Hum/Y Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S1/SvImJ * C57BL/6N * SJL/J	MGI:5700198
cn9	Cyp26b1^tm1Ptk/Cyp26b1^tm1Ptk Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4415047
cn10	Trim28^tm1.1Ipc/Trim28^tm1.1Ipc Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4948089
cn11	Trim28^tm1Fca/Trim28^tm1.1Ipc Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S2/SvPas * C57BL/6 * SJL	MGI:4948087
cn12	Plekha5^Tg(AMH-cre)1Flor/Plekha5^+ Wt1^tm1Jae/Wt1^tm2Vih	involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * SJL	MGI:3690050
cn13	Ar^tm1Chc/Y Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S/SvEv * C57BL/6 * SJL	MGI:3773622
cn14	Pofut1^tm2Pst/Pofut1^tm2Pst Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129/Sv * C57BL/6 * C57BL/6J * SJL	MGI:8213328
cn15	Dicer1^tm1Bdh/Dicer1^tm1Bdh Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129/Sv * C57BL/6 * SJL	MGI:4360936
cn16	Ar^tm1Jdz/Y Plekha5^Tg(AMH-cre)1Flor/Plekha5^+ Tg(Abpa-cre)1Cmal/0	involves: 129X1/SvJ * C57BL/6 * DBA/2 * SJL	MGI:4431084
cn17	Ar^tm1Jdz/Y Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129X1/SvJ * C57BL/6 * SJL	MGI:4431116
cn18	Hnrnph1^tm1.1Nju/Hnrnph1^tm1.1Nju Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: C57BL/6 * C57BL/6J * C57BL/6N * SJL	MGI:7768010
cn19	Mex3b^tm1.1Mbld/Mex3b^tm1.1Mbld Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: C57BL/6 * SJL	MGI:5766943
cn20	Klf4^tm1Khk/Klf4^tm1Khk Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: C57BL/6 * SJL	MGI:4365445

Genotype
MGI:5446816

ht1

• Allelic Composition: Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

abnormal male germ cell apoptosis ( J:189585 )

• intermediate

cellular

abnormal male germ cell apoptosis ( J:189585 )

• intermediate

Genotype
MGI:4431085

ht2

• Allelic Composition: Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:157337 )

N • testes have normal seminfierous tubules with a germinal layer epithelium identical to control testes

Genotype
MGI:7327644

cn3

• Allelic Composition: Aldh1a1^tm1Gdu/Aldh1a1^tm1Gdu; Aldh1a2^tm1.1Mbp/Aldh1a2^tm1.2Mbp; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129 * C57BL/6 * SJL

reproductive system

decreased Sertoli cell number ( J:324715 )

♂

abnormal spermatogenesis ( J:324715 )

♂ • block at the progression at the conversion of A spermatogonia to A1

♂ • however, injection with retinoic acid restored spermatogenesis

azoospermia ( J:324715 )

♂

male infertility ( J:324715 )

♂

endocrine/exocrine glands

decreased Sertoli cell number ( J:324715 )

♂

cellular

azoospermia ( J:324715 )

♂

Genotype
MGI:4366524

cn4

• Allelic Composition: Gja1^tm1Kwi/Gja1^tm1Kwi; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:122838 )

♂N • male mutants display normal testicular descent and genital tract development relative to control littermates

decreased male germ cell number ( J:122838 )

♂ • at P30, P60, P90, and P120, male mutants exhibit significantly reduced germ cell (spermatogonia) counts relative to control littermates

azoospermia ( J:122838 )

♂ • no sperm are detected in the cauda epididymidis of mutant males

decreased spermatid number ( J:122838 )

♂ • adult male mutants show loss and/or reduction of round or elongated spermatids

decreased spermatogonia number ( J:122838 )

♂ • adult male mutants show a significant reduction in the mean number of spermatogonia per seminiferous tubule relative to control littermates

abnormal Sertoli cell morphology ( J:122838 )

♂ • most mutant Sertoli cells display immature or aberrant features, including rounded nuclei, and absence of tubular lumina and cytoplasmic vacuoles

♂ • no mitotic figures are observed

increased Sertoli cell number ( J:122838 )

♂ • at P30, P60, P90, and P120, male mutants exhibit a significant increase in the mean number of Sertoli cells per seminiferous tubule relative to control littermates

small seminiferous tubules ( J:122838 )

♂ • adult male mutants (P170) show smaller tubules with Sertoli cell (SC)-only syndrome and intratubular SC clusters

increased Leydig cell number ( J:122838 )

♂ • a hyperplasia of interstitial Leydig cells is observed

small testis ( J:122838 )

♂ • mutant testes are significantly smaller than those of control littermates

decreased testis weight ( J:122838 )

♂ • adult male mutants (P60 to P120) show a drastic reduction in testis weight and relative testis weight (ratio between the weight of both testes to body weight) compared to control littermates

arrest of spermatogenesis ( J:122838 )

♂ • 95% of mutant seminiferous tubules exhibit an arrest of spermatogenesis at the level of spermatogonia

♂ • however, in 10 of 15 mutant males, ~5% of tubules exhibit qualitative normal spermatogenesis and few elongated spermatids

male infertility ( J:122838 )

♂ • no pups are produced when mutant males are mated with wild-type females, despite normal sexual behavior and presence of vaginal plugs

endocrine/exocrine glands

abnormal Sertoli cell morphology ( J:122838 )

♂ • most mutant Sertoli cells display immature or aberrant features, including rounded nuclei, and absence of tubular lumina and cytoplasmic vacuoles

♂ • no mitotic figures are observed

increased Sertoli cell number ( J:122838 )

♂ • at P30, P60, P90, and P120, male mutants exhibit a significant increase in the mean number of Sertoli cells per seminiferous tubule relative to control littermates

small seminiferous tubules ( J:122838 )

♂ • adult male mutants (P170) show smaller tubules with Sertoli cell (SC)-only syndrome and intratubular SC clusters

increased Leydig cell number ( J:122838 )

♂ • a hyperplasia of interstitial Leydig cells is observed

small testis ( J:122838 )

♂ • mutant testes are significantly smaller than those of control littermates

decreased testis weight ( J:122838 )

♂ • adult male mutants (P60 to P120) show a drastic reduction in testis weight and relative testis weight (ratio between the weight of both testes to body weight) compared to control littermates

cellular

decreased male germ cell number ( J:122838 )

♂ • at P30, P60, P90, and P120, male mutants exhibit significantly reduced germ cell (spermatogonia) counts relative to control littermates

azoospermia ( J:122838 )

♂ • no sperm are detected in the cauda epididymidis of mutant males

decreased spermatid number ( J:122838 )

♂ • adult male mutants show loss and/or reduction of round or elongated spermatids

decreased spermatogonia number ( J:122838 )

♂ • adult male mutants show a significant reduction in the mean number of spermatogonia per seminiferous tubule relative to control littermates

Genotype
MGI:3851809

cn5

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal testis morphology ( J:108368 )

♂

abnormal seminiferous tubule morphology ( J:108368 )

♂ • large numbers of lipid drops present at 10 days and 7 weeks

seminiferous tubule degeneration ( J:108368 )

♂ • spermatozoa still present at 7 weeks

♂ • progressive degeneration of seminiferous tubules from 9-11 weeks

decreased testis weight ( J:108368 )

♂ • testicular weight 30-40% of normal controls at 14 weeks

male infertility ( J:108368 )

♂ • 6-13 week old males mate but fail to sire offspring

endocrine/exocrine glands

abnormal testis morphology ( J:108368 )

♂

abnormal seminiferous tubule morphology ( J:108368 )

♂ • large numbers of lipid drops present at 10 days and 7 weeks

seminiferous tubule degeneration ( J:108368 )

♂ • spermatozoa still present at 7 weeks

♂ • progressive degeneration of seminiferous tubules from 9-11 weeks

decreased testis weight ( J:108368 )

♂ • testicular weight 30-40% of normal controls at 14 weeks

Genotype
MGI:3036125

cn6

• Allelic Composition: Ar^tm1Verh/Y; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6

reproductive system

abnormal spermatocyte morphology ( J:88169 )

♂ • at P50, numbers of diplotene and secondary spermatocytes were reduced to 64% of wild-type numbers

decreased male germ cell number ( J:88169 )

♂ • reduced germ cell numbers associated with increased apoptosis

azoospermia ( J:88169 )

♂ • absence of elongated spermatids

decreased elongated spermatid number ( J:88169 )

♂ • no elongated spermatids were detected

decreased round spermatid number ( J:88169 )

♂ • at P50, numbers of round spermatids were reduced to only 3% of wild-type numbers

♂ • the few round spermatids that formed appeared abnormal and failed to survive beyond stages VII-VIII

increased male germ cell apoptosis ( J:88169 )

♂ • at P50, reduced male germ cell numbers were associated with a 4-5-fold increase in germ cell apoptosis

small seminiferous tubules ( J:88169 )

♂ • significant reduction in seminiferous tubule diameter at P50

♂ • however, numbers of Sertoli cells remained essentially normal based on measurement of nuclear volume per testis

abnormal Leydig cell morphology ( J:100799 )

♂ • as expected, Leydig cell cytoplasmic volume was relatively constant up to P20 and more than doubled between P20 and P50; however, an additional 32% increase occurred between P50 and P140, such that at P140 cytoplasmic volume was 23% higher than that in controls

♂ • at P50, the volumes of mitochondria and lipid droplets were 2-fold higher than in controls; however, only the increase in lipid droplets was statistically significant

decreased Leydig cell number ( J:100799 )

♂ • although Leydig cell number was normal at P12, it was reduced by >40% at later ages (P20, P50, and P140)

♂ • notably, the temporal pattern of change in LC number was generally similar to that of controls

♂ • at P50 and P140, LC number was significantly higher than in Ar^tm1.1Verh males

♂ • immunohistochemistry and quantitative PCR for LC-specific markers revealed that steroidogenic function per LC was probably increased

small testis ( J:88169 )

♂ • testes were properly descended but small in size

♂ • normal development of epididymis, vas deferens, coagulating gland, seminal gland, and prostate gland

♂ • normal development of Leydig cells and peritubular myoid cells

decreased testis weight ( J:88169 , J:100799 )

♂ • at P50, testis weight was reduced to 28.4% of wild-type weight (J:88169)

♂ • although normal at P12, testis weight was reduced to 53% of control value at P20 and to 25-30% of control value at P50 and P140 (J:100799)

arrest of spermatogenesis ( J:88169 )

♂ • spermatogenic arrest at the late spermatocyte/spermatid stage

arrest of male meiosis ( J:88169 )

♂ • normal entry into meiosis, but progressive loss of pachytene primary spermatocytes between stages VI and XII

decreased epididymis weight ( J:88169 )

♂ • at P50, epididymis weight was reduced by 30% relative to wild-type

homeostasis/metabolism

increased circulating follicle stimulating hormone level ( J:88169 )

♂ • at P50, serum FSH leves were elevated by 34% relative to wild-type

♂ • in contrast, serum levels of testosterone and luteinizing hormone remained normal

endocrine/exocrine glands

small seminiferous tubules ( J:88169 )

♂ • significant reduction in seminiferous tubule diameter at P50

♂ • however, numbers of Sertoli cells remained essentially normal based on measurement of nuclear volume per testis

abnormal Leydig cell morphology ( J:100799 )

♂ • as expected, Leydig cell cytoplasmic volume was relatively constant up to P20 and more than doubled between P20 and P50; however, an additional 32% increase occurred between P50 and P140, such that at P140 cytoplasmic volume was 23% higher than that in controls

♂ • at P50, the volumes of mitochondria and lipid droplets were 2-fold higher than in controls; however, only the increase in lipid droplets was statistically significant

decreased Leydig cell number ( J:100799 )

♂ • although Leydig cell number was normal at P12, it was reduced by >40% at later ages (P20, P50, and P140)

♂ • notably, the temporal pattern of change in LC number was generally similar to that of controls

♂ • at P50 and P140, LC number was significantly higher than in Ar^tm1.1Verh males

♂ • immunohistochemistry and quantitative PCR for LC-specific markers revealed that steroidogenic function per LC was probably increased

small testis ( J:88169 )

♂ • testes were properly descended but small in size

♂ • normal development of epididymis, vas deferens, coagulating gland, seminal gland, and prostate gland

♂ • normal development of Leydig cells and peritubular myoid cells

decreased testis weight ( J:88169 , J:100799 )

♂ • at P50, testis weight was reduced to 28.4% of wild-type weight (J:88169)

♂ • although normal at P12, testis weight was reduced to 53% of control value at P20 and to 25-30% of control value at P50 and P140 (J:100799)

growth/size/body

growth/size/body region phenotype ( J:88169 )

♂N • growth curves of hemizygous mutant males were similar to those of wild-type males

cellular

abnormal spermatocyte morphology ( J:88169 )

♂ • at P50, numbers of diplotene and secondary spermatocytes were reduced to 64% of wild-type numbers

decreased male germ cell number ( J:88169 )

♂ • reduced germ cell numbers associated with increased apoptosis

azoospermia ( J:88169 )

♂ • absence of elongated spermatids

decreased elongated spermatid number ( J:88169 )

♂ • no elongated spermatids were detected

decreased round spermatid number ( J:88169 )

♂ • at P50, numbers of round spermatids were reduced to only 3% of wild-type numbers

♂ • the few round spermatids that formed appeared abnormal and failed to survive beyond stages VII-VIII

arrest of male meiosis ( J:88169 )

♂ • normal entry into meiosis, but progressive loss of pachytene primary spermatocytes between stages VI and XII

increased male germ cell apoptosis ( J:88169 )

♂ • at P50, reduced male germ cell numbers were associated with a 4-5-fold increase in germ cell apoptosis

Genotype
MGI:7281502

cn7

• Allelic Composition: Ptpn11^tm1Gsf/Ptpn11^tm1Gsf; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * SJL

reproductive system

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

cellular

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

endocrine/exocrine glands

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

Genotype
MGI:5700198

cn8

• Allelic Composition: Tsc22d3^tm1.1Hum/Y; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S1/SvImJ * C57BL/6N * SJL/J

reproductive system

reproductive system phenotype ( J:226675 )

♂N • deletion restricted to Sertoli cells leaves males viable and fertile with normal testicular histology, testis size, and sperm production

Genotype
MGI:4415047

cn9

• Allelic Composition: Cyp26b1^tm1Ptk/Cyp26b1^tm1Ptk; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

Loss of germ cells in adult Cyp26b1^tm1Ptk/Cyp26b1^tm1Ptk Plekha5^{Tg(AMH-cre)1Flor}/0 animals

reproductive system

decreased male germ cell number ( J:154048 )

♂ • fewer germ cells at postnatal day 0 (P0)

♂ • some seminiferous tubules are devoid of germ cells at P0

abnormal seminiferous tubule morphology ( J:154048 )

♂ • some abnormal seminiferous tubules devoid of germ cells in 3-month-old testes

♂ • other tubules contain cells from all stages of spermatogenesis

♂ • numbers of Sertoli cells are unchanged

small seminiferous tubules ( J:154048 )

♂ • reduced diameter of seminiferous tubules lacking germ cells

increased Leydig cell number ( J:154048 )

♂ • Leydig cell hyperplasia outside the seminiferous tubules lacking germ cells

small testis ( J:154048 )

♂ • smaller testes

abnormal spermatogenesis ( J:154048 )

♂ • some germ cells exit from G0 and re-enter mitosis in E16.5

♂ • 22% of the germ cells are Ki67-positive in the testes in E16.5

♂ • no significant difference in the overall number of Ki67-stained somatic cells

abnormal male meiosis ( J:154048 )

♂ • meiotic germ cells are detected in E16.5

♂ • SCP3-positive cells are detected in a subset of tubules

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:154048 )

♂ • some abnormal seminiferous tubules devoid of germ cells in 3-month-old testes

♂ • other tubules contain cells from all stages of spermatogenesis

♂ • numbers of Sertoli cells are unchanged

small seminiferous tubules ( J:154048 )

♂ • reduced diameter of seminiferous tubules lacking germ cells

increased Leydig cell number ( J:154048 )

♂ • Leydig cell hyperplasia outside the seminiferous tubules lacking germ cells

small testis ( J:154048 )

♂ • smaller testes

cellular

decreased male germ cell number ( J:154048 )

♂ • fewer germ cells at postnatal day 0 (P0)

♂ • some seminiferous tubules are devoid of germ cells at P0

abnormal male meiosis ( J:154048 )

♂ • meiotic germ cells are detected in E16.5

♂ • SCP3-positive cells are detected in a subset of tubules

Genotype
MGI:4948089

cn10

• Allelic Composition: Trim28^tm1.1Ipc/Trim28^tm1.1Ipc; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:170392 )

♂N • no defects are detected in Sertoli cell or spermatogonia proliferation at P5

abnormal spermatid morphology ( J:170392 )

♂ • spermatids fail to align at the luminal side of the seminiferous tubules at stage VII of the epithelial cycle

decreased elongated spermatid number ( J:170392 )

♂ • decrease in the number of mature spermatids

decreased male germ cell number ( J:170392 )

♂ • germ cell depletion

oligozoospermia ( J:170392 )

♂ • the caudal epididymis contains few spermatozoa

abnormal spermiation ( J:170392 )

♂ • mature spermatids are retained within the seminiferous epithelium

decreased testis weight ( J:170392 )

♂ • at 7 weeks and 12 months of age

testis degeneration ( J:170392 )

♂ • testicular degeneration

decreased litter size ( J:170392 )

♂ • sire smaller litters when crossed to wild-type females

reduced male fertility ( J:170392 )

♂ • sire fewer and smaller litters when crossed to wild-type females

endocrine/exocrine glands

decreased testis weight ( J:170392 )

♂ • at 7 weeks and 12 months of age

testis degeneration ( J:170392 )

♂ • testicular degeneration

cellular

abnormal spermatid morphology ( J:170392 )

♂ • spermatids fail to align at the luminal side of the seminiferous tubules at stage VII of the epithelial cycle

decreased male germ cell number ( J:170392 )

♂ • germ cell depletion

oligozoospermia ( J:170392 )

♂ • the caudal epididymis contains few spermatozoa

decreased elongated spermatid number ( J:170392 )

♂ • decrease in the number of mature spermatids

abnormal spermiation ( J:170392 )

♂ • mature spermatids are retained within the seminiferous epithelium

Genotype
MGI:4948087

cn11

• Allelic Composition: Trim28^tm1Fca/Trim28^tm1.1Ipc; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:170392 )

N • testes morphology is indistinguishable from controls at 7 weeks of age

Genotype
MGI:3690050

cn12

• Allelic Composition: Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺; Wt1^tm1Jae/Wt1^tm2Vih
• Genetic Background: involves: 129S4/SvJae * 129S7/SvEvBrd * C57BL/6 * SJL

reproductive system

abnormal male reproductive system morphology ( J:111787 )

♂ • in addition to reduced testes size, remainder of reproductive tract is hypoplastic

♂ • histological analysis of proximal portion of male reproductive tract shows structures with coiled morphology and folded epithelium structure of oviduct

abnormal testis morphology ( J:111787 )

♂ • at E13.5, male testicular development, including Sertoli cell location and numbers appears normal, but from E15.5 to P7, development is abnormal

abnormal seminiferous tubule morphology ( J:111787 )

♂ • testes completely lack normal tubular architecture of controls and consist primarily of sheets of eosinophilic cells

♂ • at E15.5, only a few tubule-like structures are observed

abnormal Sertoli cell development ( J:111787 )

♂

abnormal Leydig cell morphology ( J:111787 )

♂ • testes contain sheets of eosinophilic cells identified histologically as Leydig cells; these cells are observed in dense clusters interspersed with regions of fibroblast-like cells

small testis ( J:111787 )

♂ • in 7 week old males, testes size is ~10% of control wild-type littermates

abnormal secondary sex determination ( J:111787 )

• males have a uterus in addition to vas deferens, epididymis, and seminal vesicles

• histological analysis of proximal portion of male reproductive tract shows structures with coiled morphology and folded epithelium structure of oviduct

male infertility ( J:111787 )

♂ • based on aberrant structure of male testes, males are predicted to be sterile

endocrine/exocrine glands

abnormal testis morphology ( J:111787 )

♂ • at E13.5, male testicular development, including Sertoli cell location and numbers appears normal, but from E15.5 to P7, development is abnormal

abnormal seminiferous tubule morphology ( J:111787 )

♂ • testes completely lack normal tubular architecture of controls and consist primarily of sheets of eosinophilic cells

♂ • at E15.5, only a few tubule-like structures are observed

abnormal Sertoli cell development ( J:111787 )

♂

abnormal Leydig cell morphology ( J:111787 )

♂ • testes contain sheets of eosinophilic cells identified histologically as Leydig cells; these cells are observed in dense clusters interspersed with regions of fibroblast-like cells

small testis ( J:111787 )

♂ • in 7 week old males, testes size is ~10% of control wild-type littermates

Genotype
MGI:3773622

cn13

• Allelic Composition: Ar^tm1Chc/Y; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

reproductive system

decreased male germ cell number ( J:89886 )

♂ • mutant testes have fewer proliferating spermatogonia relative to wild-type

♂ • there are increased numbers of apoptotic pachytene and metaphase spermatocytes compared to wild-type

abnormal meiosis ( J:118270 )

♂ • testes show a 3-fold increase in diploid cells, 2-fold increase in tetraploid cells and an 11-fold reduction in haploid cells

abnormal seminiferous tubule morphology ( J:89886 , J:118270 )

♂ • tubules display poor germ cell differentiation, and reduced cellularity, with most germ cell differentiation ceasing at the diplotene stage (J:89886)

♂ • mutant testes show less active cell proliferation per tubule, and fewer proliferative tubules per testis (J:89886)

♂ • no lumen is observed (J:118270)

small testis ( J:118270 )

♂ • testes are normally descended but only attain 23.4% of that in wild-type males

decreased testis weight ( J:89886 )

♂ • size of testes is reduced compared to wild-type males, with weights only one-third of wild-type testes

abnormal spermatogenesis ( J:89886 )

♂ • mice have an increased number of tetraploid cells and a reduction in cells with a haploid DNA content

azoospermia ( J:89886 , J:118270 )

♂ • analysis of epididymes detected only debris instead of normal, motile sperm as observed in wild-type males (J:89886)

♂ • no live sperm are found in epididymis (J:118270)

arrest of male meiosis ( J:89886 , J:118270 )

♂ • diploid to tetraploid germ cell ratio indicates spermatogenic arrest before the first meiosis (J:89886)

♂ • little evidence of meiosis is observed, with no spermatids or spermatozoa, elongated or round detected in the testes (J:89886)

♂ • germ cell development stops at pachytene/diplotene primary spermatocyte stage of the first meiosis division (J:118270)

male infertility ( J:89886 , J:118270 )

♂ • 8-week old males fail to impregnate wild-type females in 3 successive 2-week pairings; vaginal plugs were detected but no pregnancies resulted (J:89886)

♂ • in three successive 2-week pairings with wild-type females, 14-week old males fail to impregnated the females; vaginal plugs were detected in females after mating (J:118270)

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:89886 , J:118270 )

♂ • tubules display poor germ cell differentiation, and reduced cellularity, with most germ cell differentiation ceasing at the diplotene stage (J:89886)

♂ • mutant testes show less active cell proliferation per tubule, and fewer proliferative tubules per testis (J:89886)

♂ • no lumen is observed (J:118270)

small testis ( J:118270 )

♂ • testes are normally descended but only attain 23.4% of that in wild-type males

decreased testis weight ( J:89886 )

♂ • size of testes is reduced compared to wild-type males, with weights only one-third of wild-type testes

homeostasis/metabolism

decreased circulating testosterone level ( J:89886 , J:118270 )

♂ • mutant males have lower serum testosterone levels than wild-type males (J:89886)

♂ • significantly decreased relative to wild-type males (J:118270)

increased circulating follicle stimulating hormone level ( J:89886 )

♂ • levels are marginally (10%) increased compared to control males

increased circulating luteinizing hormone level ( J:89886 )

♂ • LH levels are increased in serum compared to wild-type males

cellular

decreased male germ cell number ( J:89886 )

♂ • mutant testes have fewer proliferating spermatogonia relative to wild-type

♂ • there are increased numbers of apoptotic pachytene and metaphase spermatocytes compared to wild-type

azoospermia ( J:89886 , J:118270 )

♂ • analysis of epididymes detected only debris instead of normal, motile sperm as observed in wild-type males (J:89886)

♂ • no live sperm are found in epididymis (J:118270)

abnormal meiosis ( J:118270 )

♂ • testes show a 3-fold increase in diploid cells, 2-fold increase in tetraploid cells and an 11-fold reduction in haploid cells

arrest of male meiosis ( J:89886 , J:118270 )

♂ • diploid to tetraploid germ cell ratio indicates spermatogenic arrest before the first meiosis (J:89886)

♂ • little evidence of meiosis is observed, with no spermatids or spermatozoa, elongated or round detected in the testes (J:89886)

♂ • germ cell development stops at pachytene/diplotene primary spermatocyte stage of the first meiosis division (J:118270)

Genotype
MGI:8213328

cn14

• Allelic Composition: Pofut1^tm2Pst/Pofut1^tm2Pst; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * C57BL/6J * SJL

reproductive system

reproductive system phenotype ( J:185823 )

♂N • at 6-8 months of age, male mice exhibit normal fertility and spermatogenesis with no significant differences in litter size, cauda epididymal sperm count, testis-to-body weight ratio, or average number of apoptotic cells per 100 round tubule cross-sections relative to control males

Genotype
MGI:4360936

cn15

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129/Sv * C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:145178 )

♂N • adult males show no differences in mounting and copulatory activity or in testicular descent and masculinization of internal reproductive organs (seminal vesicles and prostate) relative to control littermates

abnormal male germ cell morphology ( J:145178 )

♂ • at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts

decreased male germ cell number ( J:145178 )

♂ • at P60, mutant male germ cells are severely disorganized and reduced in number

♂ • by 6 months of age, the few remaining tubes are almost completely devoid of germ cells

azoospermia ( J:145178 )

♂ • at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts

decreased spermatid number ( J:145178 )

♂ • at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes

decreased elongated spermatid number ( J:145178 )

♂

decreased round spermatid number ( J:145178 )

♂

increased male germ cell apoptosis ( J:145178 )

♂ • significant male germ cell apoptosis is noted at P15 and P21

♂ • by P42, mutant male germ cells exhibit extensive apoptosis

increased Sertoli cell proliferation ( J:145178 )

♂ • a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation

abnormal seminiferous tubule epithelium morphology ( J:145178 )

♂ • at P60, the mutant seminiferous epithelium appears disorganized

abnormal Sertoli cell morphology ( J:145178 )

♂ • as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen

♂ • at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape

♂ • a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation

♂ • significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells

♂ • by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed

ectopic Sertoli cells ( J:145178 )

♂ • as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery

small seminiferous tubules ( J:145178 )

♂ • at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen

seminiferous tubule degeneration ( J:145178 )

♂ • as early as P5, numerous pycnotic cells are detected within mutant tubes

♂ • at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen

♂ • by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology

increased Leydig cell number ( J:145178 )

♂ • Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age

♂ • however, no significant differences in testicular testosterone levels are observed from P0 to P60

small testis ( J:145178 )

♂ • at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes

♂ • by 6 months of age, mutant testis size is only 5% of that in control littermates

decreased testis weight ( J:145178 )

♂ • at P60, mutant males show a 90% reduction in testis weight relative to control littermates

testis degeneration ( J:145178 )

♂ • severe testicular degeneration is noted at P60 and worsens upon aging

♂ • by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes

abnormal spermatogenesis ( J:145178 )

♂ • at P60, mutant males show severe spermatogenic defects including vacuolization, Sertoli-cell-only tubes, tubes with spermatogenic arrest at an early post-meiotic stage, and disorganization of the seminiferous epithelium

male infertility ( J:145178 )

♂ • mutant males fail to produce any offspring during a 6-month mating period with wild-type C57BL/6J females

endocrine/exocrine glands

increased Sertoli cell proliferation ( J:145178 )

♂ • a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation

abnormal seminiferous tubule epithelium morphology ( J:145178 )

♂ • at P60, the mutant seminiferous epithelium appears disorganized

abnormal Sertoli cell morphology ( J:145178 )

♂ • as early as P5, mutant males display Sertoli cell nuclear mislocalization with almost complete absence of lumen

♂ • at P15, mutant Sertoli cell nuclei display an abnormal circular rather than flattened triangular shape

♂ • a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation

♂ • significant Sertoli cell apoptosis is noted at P5; however, by P21, apoptotic cells are almost exclusively germ cells

♂ • by 3 months of age, obvious defects in Sertoli cell cyto-architecture and polarity are observed

ectopic Sertoli cells ( J:145178 )

♂ • as early as P5, mutant Sertoli cell nuclei are mislocalized in the center of seminiferous tubes instead of the periphery

small seminiferous tubules ( J:145178 )

♂ • at P60, mutant seminiferous tubules are reduced in diameter and devoid of lumen

seminiferous tubule degeneration ( J:145178 )

♂ • as early as P5, numerous pycnotic cells are detected within mutant tubes

♂ • at P42, almost all mutant tubes have become severely vacuolized; however, a few less severely affected tubes display a lumen

♂ • by 3 months of age, most seminiferous tubules have degenerated into Sertoli-cell-only tubes with a severely impaired Sertoli cell morphology

increased Leydig cell number ( J:145178 )

♂ • Leydig cell hyperplasia is already noted at P5, persists throughout adulthood, and becomes massive by 6 months of age

♂ • however, no significant differences in testicular testosterone levels are observed from P0 to P60

small testis ( J:145178 )

♂ • at P15 and P60, mutant testes show a 80% and 90% reduction in size, respectively, relative to control testes

♂ • by 6 months of age, mutant testis size is only 5% of that in control littermates

decreased testis weight ( J:145178 )

♂ • at P60, mutant males show a 90% reduction in testis weight relative to control littermates

testis degeneration ( J:145178 )

♂ • severe testicular degeneration is noted at P60 and worsens upon aging

♂ • by 6 months of age, mutant testes have degenerated into a mass of interstitial cells containing rare remaining tubes

cellular

abnormal male germ cell morphology ( J:145178 )

♂ • at P60, numerous exfoliated germ cells are detected in the lumen of mutant epididymal ducts

decreased male germ cell number ( J:145178 )

♂ • at P60, mutant male germ cells are severely disorganized and reduced in number

♂ • by 6 months of age, the few remaining tubes are almost completely devoid of germ cells

azoospermia ( J:145178 )

♂ • at P60, mutant males show complete absence of mature spermatozoa in testes and epididymal ducts

decreased spermatid number ( J:145178 )

♂ • at P42, round spermatids are severely reduced in number while elongated spermatids are entirely absent in mutant testes

decreased elongated spermatid number ( J:145178 )

♂

decreased round spermatid number ( J:145178 )

♂

increased male germ cell apoptosis ( J:145178 )

♂ • significant male germ cell apoptosis is noted at P15 and P21

♂ • by P42, mutant male germ cells exhibit extensive apoptosis

increased Sertoli cell proliferation ( J:145178 )

♂ • a 1.25-, 1.5-, and 2.6-fold increase in Sertoli cell proliferation is observed at P0, P5, and P15, respectively, suggesting delayed Sertoli cell maturation

Genotype
MGI:4431084

cn16

• Allelic Composition: Ar^tm1Jdz/Y; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺; Tg(Abpa-cre)1Cmal/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA/2 * SJL

reproductive system

decreased testis weight ( J:157337 )

♂ • at 9 weeks of age, testis weights are similar to those of homozygous Tg(AMH-cre)1Flor or homozygous Tg(Abpa-cre)1Cmal/ Ar^tm1Jdz double mutants

endocrine/exocrine glands

decreased testis weight ( J:157337 )

♂ • at 9 weeks of age, testis weights are similar to those of homozygous Tg(AMH-cre)1Flor or homozygous Tg(Abpa-cre)1Cmal/ Ar^tm1Jdz double mutants

Genotype
MGI:4431116

cn17

• Allelic Composition: Ar^tm1Jdz/Y; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * SJL

growth/size/body

growth/size/body region phenotype ( J:157337 )

♂N • total body weights of males are equivalent to wild-type males

reproductive system

small seminiferous tubules ( J:157337 )

♂ • tubules with smaller diameters are observed at 9 weeks

♂ • at 9 weeks total Sertoli cell numbers are same as in controls

abnormal Leydig cell morphology ( J:157337 )

♂ • at 9 weeks, interstitial Leydig cells display hypertrophy and accumulation of lipid droplets

♂ • adult Leydig cells are present in testes at 9 weeks

Leydig cell hypertrophy ( J:157337 )

♂ • Leydig cells display hypertrophy at 9 weeks

decreased testis weight ( J:157337 )

♂ • at 5 or 10 days, testis weights are normal, but testis weights at 3 weeks are significantly lower (15.9 mg) than control males (24.9-27 mg)

arrest of spermatogenesis ( J:157337 )

♂ • spermatogenic arrest predominantly at meiotic stage with no elongated spermatids is observed at 9 weeks

male infertility ( J:157337 )

♂

endocrine/exocrine glands

small seminiferous tubules ( J:157337 )

♂ • tubules with smaller diameters are observed at 9 weeks

♂ • at 9 weeks total Sertoli cell numbers are same as in controls

abnormal Leydig cell morphology ( J:157337 )

♂ • at 9 weeks, interstitial Leydig cells display hypertrophy and accumulation of lipid droplets

♂ • adult Leydig cells are present in testes at 9 weeks

Leydig cell hypertrophy ( J:157337 )

♂ • Leydig cells display hypertrophy at 9 weeks

decreased testis weight ( J:157337 )

♂ • at 5 or 10 days, testis weights are normal, but testis weights at 3 weeks are significantly lower (15.9 mg) than control males (24.9-27 mg)

Genotype
MGI:7768010

cn18

• Allelic Composition: Hnrnph1^tm1.1Nju/Hnrnph1^tm1.1Nju; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * SJL

reproductive system

oligozoospermia ( J:333262 )

♂ • adults show reduced numbers of spermatocytes and spermatids and no detectable mature spermatozoa in seminiferous tubules and cauda epididymis

decreased spermatid number ( J:333262 )

♂ • decrease in spermatids in adults

abnormal spermatocyte morphology ( J:333262 )

♂ • decrease in spermatocytes in adults

abnormal male meiosis ( J:333262 )

♂ • a higher proportion of spermatocytes show an abnormal gamma-H2A.X distribution, indicating the DNA damage response remains active in synapsed homologs of pachytene spermatocytes

♂ • pachytene spermatocytes show abnormal double-strand DNA break (DSB) repair

♂ • pachytene and diplotene spermatocytes are reduced indicating developmental retardation of pachytene spermatocytes

increased male germ cell apoptosis ( J:333262 )

♂ • the number of apoptotic cells in testis is increased even at the early P14 stage, suggesting dystrophy of the developing spermatocytes during the first wave of spermatogenesis

abnormal seminiferous tubule morphology ( J:333262 )

♂ • F-actin is disorganized in seminiferous tubules

abnormal Sertoli cell barrier morphology ( J:333262 )

♂ • abnormal Sertoli cell morphology and blood-testis barrier structure with large irregular cavities is seen in the seminiferous epithelium

♂ • basal tight junction proteins (N-cadherin and beta-catenin) and ectoplasmic specialization protein (ZO-1) are found beyond the basement membrane of seminiferous tubules and diffusely present at the blood-testis barrier, extending towards the lumen

abnormal Sertoli cell morphology ( J:333262 )

♂ • cytoskeleton of Sertoli cells shows disruption of microtubular arrangement and actin organization

♂ • length of vimentin filaments in Sertoli cells in seminiferous tubules is shorter

abnormal ectoplasmic specialization morphology ( J:333262 )

♂ • the structure of apical ectoplasmic specialization is disrupted

small seminiferous tubules ( J:333262 )

♂ • developing testes show decreased diameter of seminiferous tubules from P21 onwards

small testis ( J:333262 )

♂

decreased testis weight ( J:333262 )

♂ • ratio of testis weight to body weight is reduced from P21 onwards

abnormal Sertoli cell barrier function ( J:333262 )

♂ • biotin tracer permeates into seminiferous tubules indicating disrupted blood-testis barrier

arrest of spermatogenesis ( J:333262 )

♂ • spermatogenesis is arrested in step 15 spermatids

♂ • however, development and differentiation of spermatogonia both in juvenile and adult mice are not affected

abnormal epididymis morphology ( J:333262 )

♂ • a large number of round spermatids and a few spermatocytes are prematurely sloughed into cauda epididymis at P28 and P60

male infertility ( J:333262 )

♂ • males never produce any pups

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:333262 )

♂ • F-actin is disorganized in seminiferous tubules

abnormal Sertoli cell barrier morphology ( J:333262 )

♂ • abnormal Sertoli cell morphology and blood-testis barrier structure with large irregular cavities is seen in the seminiferous epithelium

♂ • basal tight junction proteins (N-cadherin and beta-catenin) and ectoplasmic specialization protein (ZO-1) are found beyond the basement membrane of seminiferous tubules and diffusely present at the blood-testis barrier, extending towards the lumen

abnormal Sertoli cell morphology ( J:333262 )

♂ • cytoskeleton of Sertoli cells shows disruption of microtubular arrangement and actin organization

♂ • length of vimentin filaments in Sertoli cells in seminiferous tubules is shorter

abnormal ectoplasmic specialization morphology ( J:333262 )

♂ • the structure of apical ectoplasmic specialization is disrupted

small seminiferous tubules ( J:333262 )

♂ • developing testes show decreased diameter of seminiferous tubules from P21 onwards

small testis ( J:333262 )

♂

decreased testis weight ( J:333262 )

♂ • ratio of testis weight to body weight is reduced from P21 onwards

abnormal Sertoli cell barrier function ( J:333262 )

♂ • biotin tracer permeates into seminiferous tubules indicating disrupted blood-testis barrier

cellular

oligozoospermia ( J:333262 )

♂ • adults show reduced numbers of spermatocytes and spermatids and no detectable mature spermatozoa in seminiferous tubules and cauda epididymis

decreased spermatid number ( J:333262 )

♂ • decrease in spermatids in adults

abnormal spermatocyte morphology ( J:333262 )

♂ • decrease in spermatocytes in adults

abnormal male meiosis ( J:333262 )

♂ • a higher proportion of spermatocytes show an abnormal gamma-H2A.X distribution, indicating the DNA damage response remains active in synapsed homologs of pachytene spermatocytes

♂ • pachytene spermatocytes show abnormal double-strand DNA break (DSB) repair

♂ • pachytene and diplotene spermatocytes are reduced indicating developmental retardation of pachytene spermatocytes

increased male germ cell apoptosis ( J:333262 )

♂ • the number of apoptotic cells in testis is increased even at the early P14 stage, suggesting dystrophy of the developing spermatocytes during the first wave of spermatogenesis

Genotype
MGI:5766943

cn19

• Allelic Composition: Mex3b^tm1.1Mbld/Mex3b^tm1.1Mbld; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

mortality/aging ( J:213588 )

N • mice exhibit no perinatal lethality, unlike Mex3b^tm1.2Mbld homozygotes

growth/size/body

growth/size/body region phenotype ( J:213588 )

N • mice exhibit no defect in postnatal growth, unlike Mex3b^tm1.2Mbld homozygotes

reproductive system

abnormal seminiferous tubule morphology ( J:213588 )

♂ • at 1 and 2 months of age, mice exhibit obstructed seminiferous tubules at a ratio that is very similar to that seen in male Mex3b^tm1.2Mbld homozygotes

♂ • tubule lumens are obstructed at stages V and VIII whereas those of control mice are empty (stages VIII and XI)

increased Sertoli cell number ( J:213588 )

♂ • at 1 and 2 months of age, mice exhibit a decreased ratio between germ and Sertoli cells, in the same order of magnitude as that seen in Mex3b^tm1.2Mbld homozygotes

abnormal Sertoli cell barrier function ( J:213588 )

♂ • mice exhibit altered permeability of the blood-testis barrier (BTB) leading to the production of anti-sperm antibodies

reduced male fertility ( J:213588 )

♂ • upon breeding with Mex3b^tm1.1Mbld female homozygotes, males exhibit a reduction in fertility similar to that observed upon breeding of Mex3b^tm1.2Mbld male homozygotes with wild-type females

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:213588 )

♂ • at 1 and 2 months of age, mice exhibit obstructed seminiferous tubules at a ratio that is very similar to that seen in male Mex3b^tm1.2Mbld homozygotes

♂ • tubule lumens are obstructed at stages V and VIII whereas those of control mice are empty (stages VIII and XI)

increased Sertoli cell number ( J:213588 )

♂ • at 1 and 2 months of age, mice exhibit a decreased ratio between germ and Sertoli cells, in the same order of magnitude as that seen in Mex3b^tm1.2Mbld homozygotes

abnormal Sertoli cell barrier function ( J:213588 )

♂ • mice exhibit altered permeability of the blood-testis barrier (BTB) leading to the production of anti-sperm antibodies

immune system

increased anti-sperm antibody level ( J:213588 )

♂ • mice exhibit increased levels of anti-sperm cell antibodies in the serum, indicating that BTB integrity is impaired

Genotype
MGI:4365445

cn20

• Allelic Composition: Klf4^tm1Khk/Klf4^tm1Khk; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: C57BL/6 * SJL

reproductive system

reproductive system phenotype ( J:132612 )

N • mutant males show normal postnatal testis weights, with no significant differences in the ratio of testis weight to body weight or in Sertoli cell proliferation relative to control littermates

N • notably, adult mutant males are fertile and yield litters of normal size and frequency relative to controls, despite reduced serum testosterone levels

abnormal seminiferous tubule epithelium morphology ( J:132612 )

♂ • at P18, mutant tubules exhibit a disorganized germinal epithelium with numerous vacuoles and no lumen

♂ • however, no differences with regard to vacuolization of the cytoplasm or (dis-) organization of the germinal epithelium are noted in adult mutant tubules relative to controls, indicating that the phenotype observed at P18 is transient

♂ • moreover, no significant differences are observed between the % of TUNEL-positive mutant tubules vs control tubules

abnormal seminiferous tubule size ( J:132612 )

♂ • whereas at P18 mutant tubules display a slightly, yet significantly increased diameter, at P20 mutant tubules exhibit a significantly reduced average diameter relative to control tubules

abnormal Sertoli cell development ( J:132612 )

♂ • at P18, mutant Sertoli cells display a developmental delay in lumen formation with only 32% of mutant tubules exhibiting a lumen vs 75% of control tubules

♂ • at P20, only 50% of mutant tubules display a lumen vs 87% of control tubules

abnormal testes secretion ( J:132612 )

♂ • gene expression profiling revealed differential expression of genes known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggesting impaired apical secretion of Sertoli cells

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:132612 )

♂ • at P18, mutant tubules exhibit a disorganized germinal epithelium with numerous vacuoles and no lumen

♂ • however, no differences with regard to vacuolization of the cytoplasm or (dis-) organization of the germinal epithelium are noted in adult mutant tubules relative to controls, indicating that the phenotype observed at P18 is transient

♂ • moreover, no significant differences are observed between the % of TUNEL-positive mutant tubules vs control tubules

abnormal seminiferous tubule size ( J:132612 )

♂ • whereas at P18 mutant tubules display a slightly, yet significantly increased diameter, at P20 mutant tubules exhibit a significantly reduced average diameter relative to control tubules

abnormal Sertoli cell development ( J:132612 )

♂ • at P18, mutant Sertoli cells display a developmental delay in lumen formation with only 32% of mutant tubules exhibiting a lumen vs 75% of control tubules

♂ • at P20, only 50% of mutant tubules display a lumen vs 87% of control tubules

abnormal testes secretion ( J:132612 )

♂ • gene expression profiling revealed differential expression of genes known to play roles during vesicle transport and fusion or for maintenance of the differentiated cell state, suggesting impaired apical secretion of Sertoli cells

homeostasis/metabolism

decreased circulating testosterone level ( J:132612 )

• at P56-P365, adult mutant males exhibit significantly reduced serum testosterone levels relative to control males

• in contrast, adult serum follicle stimulation hormone (FSH) and triiodothyronine (T3) levels remain relatively unaffected