Phenotypes associated with this allele

• Allele Symbol: Ct55^em2Xdzg
• Allele Name: endonuclease-mediated mutation 2, Xiao-Dong Zhang
• Allele ID: MGI:7494107
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ct55^em2Xdzg/Ct55^em2Xdzg	C57BL/6-Ct55^em2Xdzg	MGI:7506440
ot2	Ct55^em2Xdzg/Y	C57BL/6-Ct55^em2Xdzg	MGI:7506441

Genotype
MGI:7506440

hm1

• Allelic Composition: Ct55^em2Xdzg/Ct55^em2Xdzg
• Genetic Background: C57BL/6-Ct55^em2Xdzg

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

reproductive system

reproductive system phenotype ( J:337211 )

♀N • female mice are fertile

Genotype
MGI:7506441

ot2

• Allelic Composition: Ct55^em2Xdzg/Y
• Genetic Background: C57BL/6-Ct55^em2Xdzg

mortality/aging

early reproductive senescence ( J:337211 )

♂ • males show a progressive decline in the average number of litters per mouse and the average number of pups per litter from 8 to 16 weeks of age and become totally infertile at ~32 weeks of age, indicating accelerated infertility with age

reproductive system

reproductive system phenotype ( J:337211 )

♂N • males show no significant differences in the size and weight of testes and epididymides or testis histology at 8, 16 and 32 weeks of age relative to wild-type controls

♂N • male meiosis is normal, as confirmed by a spermatocyte spreading assay

early reproductive senescence ( J:337211 )

♂ • males show a progressive decline in the average number of litters per mouse and the average number of pups per litter from 8 to 16 weeks of age and become totally infertile at ~32 weeks of age, indicating accelerated infertility with age

abnormal spermatogenesis ( J:337211 )

♂ • testes show increased signals of ribosome and endoplasmic reticulum-associated proteins, indicating that autophagic removal of excessive cytoplasmic materials is impaired during spermatogenesis

♂ • testes show increased expression of LC3 and p62 and reduced expression of autophagy-associated proteins LAMP2 and GABARAP

abnormal sperm mitochondrial sheath morphology ( J:337211 )

♂ • both testicular spermatids and epididymal spermatozoa show aberrant mitochondria with dilated intermembrane spaces

abnormal sperm fibrous sheath morphology ( J:337211 )

♂ • both testicular spermatids and epididymal spermatozoa show an incomplete fibrous sheath

oligozoospermia ( J:337211 )

♂ • number of spermatozoa is progressively reduced in different segments of the epididymis (including the proximal and distal cauda) from 8 to 32 weeks of age

abnormal acrosome morphology ( J:337211 )

♂ • number of acrosomal granules (AG) is abnormal (missing or multiple) or AGs are ectopic or morphologically abnormal

abnormal acrosome assembly ( J:337211 )

♂ • TEM analysis showed defects in acrosome development, including missing or abnormal Golgi apparatus and ectopic or abnormal acrosomal granule (AG) number, resulting in an aberrant acrosome structure in the maturation phase

abnormal spermatid morphology ( J:337211 )

♂ • some round spermatids exhibit an absent or disordered Golgi apparatus

abnormal spermiogenesis ( J:337211 )

♂ • both testicular spermatids and epididymal spermatozoa show excessive residual cytoplasm, indicating a defect in cytoplasm removal

abnormal sperm individualization ( J:337211 )

♂ • sperm are aggregated into bundles or sperm flagella are inseparable

♂ • both testicular spermatids and epididymal spermatozoa show impaired individualization

abnormal epididymis morphology ( J:337211 )

♂ • number of spermatozoa is progressively reduced in different segments of the epididymis (including the initial segment, caput, distal caput, and proximal and distal cauda) with increasing age

male infertility ( J:337211 )

♂ • males become completely infertile at ~32 weeks of age

decreased fertilization frequency ( J:337211 )

♂ • in an IVF assay using cumulus-intact oocytes, the zygotic formation rate, 2-cell embryo rate, and blastocyst rate are all significantly lower than in wild-type controls

♂ • reduced fertilization rate is related to impaired cumulus cell dispersal

♂ • however, no significant differences are observed with cumulus-free oocytes

abnormal sperm physiology ( J:337211 )

♂ • in a cumulus cell dispersal assay, sperm show an impaired capacity to penetrate the cumulus-oocyte complex (COC)

♂ • cumulus cell dispersal is significantly delayed in the presence of cauda epididymal sperm or sperm protein extracts

♂ • however, the COC dispersal ability of sperm or sperm protein extracts is restored by adding purified human sperm hyaluronidase to the IVF medium

decreased sperm progressive motility ( J:337211 )

♂ • cauda epididymal spermatozoa show a significant decline in the % of progressive motility

asthenozoospermia ( J:337211 )

♂ • CASA analysis showed a significant decline in all sperm motility parameters, including curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), amplitude of lateral head displacement (ALH), linearity (LIN), wobble (WOB = VAP/VCL), straightness (STR = VSL/VAP), and beat-cross frequency (BCF)

♂ • cauda epididymal spermatozoa are almost immotile by ~32 weeks of age

♂ • SpermQ analysis showed that the lateral swing amplitude of sperm flagella is significantly reduced when the head is fixed by polylysine

cellular

abnormal sperm mitochondrial sheath morphology ( J:337211 )

♂ • both testicular spermatids and epididymal spermatozoa show aberrant mitochondria with dilated intermembrane spaces

abnormal sperm fibrous sheath morphology ( J:337211 )

♂ • both testicular spermatids and epididymal spermatozoa show an incomplete fibrous sheath

oligozoospermia ( J:337211 )

♂ • number of spermatozoa is progressively reduced in different segments of the epididymis (including the proximal and distal cauda) from 8 to 32 weeks of age

abnormal acrosome morphology ( J:337211 )

♂ • number of acrosomal granules (AG) is abnormal (missing or multiple) or AGs are ectopic or morphologically abnormal

abnormal acrosome assembly ( J:337211 )

♂ • TEM analysis showed defects in acrosome development, including missing or abnormal Golgi apparatus and ectopic or abnormal acrosomal granule (AG) number, resulting in an aberrant acrosome structure in the maturation phase

abnormal spermatid morphology ( J:337211 )

♂ • some round spermatids exhibit an absent or disordered Golgi apparatus

abnormal Golgi apparatus morphology ( J:337211 )

♂ • some round spermatids exhibit an absent or disordered Golgi apparatus

impaired autophagy ( J:337211 )

♂ • testes show increased signals of ribosome and endoplasmic reticulum-associated proteins, indicating that autophagic removal of excessive cytoplasmic materials is impaired during spermatogenesis

♂ • testes show increased expression of LC3 and p62 and reduced expression of autophagy-associated proteins LAMP2 and GABARAP

decreased sperm progressive motility ( J:337211 )

♂ • cauda epididymal spermatozoa show a significant decline in the % of progressive motility

asthenozoospermia ( J:337211 )

♂ • CASA analysis showed a significant decline in all sperm motility parameters, including curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), amplitude of lateral head displacement (ALH), linearity (LIN), wobble (WOB = VAP/VCL), straightness (STR = VSL/VAP), and beat-cross frequency (BCF)

♂ • cauda epididymal spermatozoa are almost immotile by ~32 weeks of age

♂ • SpermQ analysis showed that the lateral swing amplitude of sperm flagella is significantly reduced when the head is fixed by polylysine

homeostasis/metabolism

impaired autophagy ( J:337211 )

♂ • testes show increased signals of ribosome and endoplasmic reticulum-associated proteins, indicating that autophagic removal of excessive cytoplasmic materials is impaired during spermatogenesis

♂ • testes show increased expression of LC3 and p62 and reduced expression of autophagy-associated proteins LAMP2 and GABARAP