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Phenotypes Associated with This Genotype
Genotype
MGI:6870513
Allelic
Composition
Alpltm1(cre)Nagy/Alpl+
Atg7tm1Tchi/Atg7tm1Tchi
Genetic
Background
involves: 129 * C57BL/6 * C57BL/6NCrlj * CBA/JNCrlj
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alpltm1(cre)Nagy mutation (6 available); any Alpl mutation (352 available)
Atg7tm1Tchi mutation (3 available); any Atg7 mutation (51 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• total number of spermatozoa in the cauda epididymis is severely reduced
• acrosomes fail to acquire the characteristic crescent moon shape and display various defects, including mislocalization, deformation and fragmentation
• fragmented acrosomes are observed in the Golgi and cap phases
• acrosome shrinkage is detected in the cap phase due to accumulated proacrosomal vesicles derived from the Golgi apparatus
• vacuolated or irregularly shaped acrosomes are seen in subsequent stages of spermiogenesis
• acrosome biogenesis is disrupted starting in the Golgi phase: multiple small vesicles are localized to the perinuclear region without fusing with each other in ~30% of Golgi-phase spermatids
• in the cap-phase, the acrosome fails to spread normally along the nucleus and many proacrosomal vesicles accumulate in the concave region near the trans-Golgi stacks in ~27% of spermatids
• in the acrosome and maturation phases, irregular or roughly round acrosomes are found in ~24% of spermatids and the nucleus shows less chromatin condensation and/or impaired nuclear elongation
• defect in acrosome formation is most likely due to the failure of Golgi-derived proacrosomal vesicle fusion and/or membrane trafficking
• multiple small vesicles are localized to the perinuclear region without fusing with each other in ~30% of Golgi-phase spermatids
• TEM images show two proacrosomal centers present around the nucleus
• 26.80% of sperm exhibit irregularly shaped round heads, only seen in 0.42% of control sperm
• in the acrosome and maturation phases, the nucleus neighboring malformed acrosomes shows less chromatin condensation and/or impaired nuclear elongation, resulting in round or irregularly shaped nuclei
• TUNEL staining showed a significantly higher % of apoptotic cells in the seminiferous tubules (0.47% versus 0.04% in control tubules)
• seminiferous tubule structure appears disorganized: 36.67% of tubules contain large vacuoles in their lumen versus only 1.33% of control tubules
• TUNEL staining showed a significantly higher % of apoptotic cells in the seminiferous tubules (0.47% versus 0.04% in control tubules)
• however, seminiferous tubule diameter is normal
• testis size is significantly smaller than that in control males
• testis weight is significantly lower than that in control males
• acrosome biogenesis is highly disrupted during early stages of spermiogenesis
• many detached premature germ cells and abnormal spermatozoa are detected in the cauda epididymis
• males are almost completely infertile: when mated to wild-type females for a 2-month period, pregnancy rate is only 8.14% versus 87.01% for control males
• in vivo fertilization capacity of spermatozoa is impaired; when male mice are mated with wild-type females, no 2-cell embryos are obtained
• however, this defect is successfully rescued by intracytoplasmic sperm injections
• in vitro, the rate of A23187-induced acrosome reaction is severely reduced: after induction, only 38.67% of spermatozoa show loss of their PSA-positive structures versus 63.87% in control sperm, suggesting failure to release acrosomal contents
• however, the rate of spontaneous acrosome reaction is relatively normal

cellular
• total number of spermatozoa in the cauda epididymis is severely reduced
• acrosomes fail to acquire the characteristic crescent moon shape and display various defects, including mislocalization, deformation and fragmentation
• fragmented acrosomes are observed in the Golgi and cap phases
• acrosome shrinkage is detected in the cap phase due to accumulated proacrosomal vesicles derived from the Golgi apparatus
• vacuolated or irregularly shaped acrosomes are seen in subsequent stages of spermiogenesis
• acrosome biogenesis is disrupted starting in the Golgi phase: multiple small vesicles are localized to the perinuclear region without fusing with each other in ~30% of Golgi-phase spermatids
• in the cap-phase, the acrosome fails to spread normally along the nucleus and many proacrosomal vesicles accumulate in the concave region near the trans-Golgi stacks in ~27% of spermatids
• in the acrosome and maturation phases, irregular or roughly round acrosomes are found in ~24% of spermatids and the nucleus shows less chromatin condensation and/or impaired nuclear elongation
• defect in acrosome formation is most likely due to the failure of Golgi-derived proacrosomal vesicle fusion and/or membrane trafficking
• multiple small vesicles are localized to the perinuclear region without fusing with each other in ~30% of Golgi-phase spermatids
• TEM images show two proacrosomal centers present around the nucleus
• 26.80% of sperm exhibit irregularly shaped round heads, only seen in 0.42% of control sperm
• in the acrosome and maturation phases, the nucleus neighboring malformed acrosomes shows less chromatin condensation and/or impaired nuclear elongation, resulting in round or irregularly shaped nuclei
• autophagic flux is disrupted in the testis, as indicated by a 1.5-fold increase in polyubiquitinated protein level and accumulation of the autophagic substrate SQSTM1/p62 and of LC3-I but not the membrane-associated form LC3-II
• TUNEL staining showed a significantly higher % of apoptotic cells in the seminiferous tubules (0.47% versus 0.04% in control tubules)

homeostasis/metabolism
• autophagic flux is disrupted in the testis, as indicated by a 1.5-fold increase in polyubiquitinated protein level and accumulation of the autophagic substrate SQSTM1/p62 and of LC3-I but not the membrane-associated form LC3-II

endocrine/exocrine glands
• seminiferous tubule structure appears disorganized: 36.67% of tubules contain large vacuoles in their lumen versus only 1.33% of control tubules
• TUNEL staining showed a significantly higher % of apoptotic cells in the seminiferous tubules (0.47% versus 0.04% in control tubules)
• however, seminiferous tubule diameter is normal
• testis size is significantly smaller than that in control males
• testis weight is significantly lower than that in control males


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
12/17/2024
MGI 6.24
The Jackson Laboratory