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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Pfn4em1Hsc
endonuclease-mediated mutation 1, Hubert Schorle
MGI:6718278
Summary 1 genotype
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Pfn4em1Hsc/Pfn4em1Hsc C57BL/6J-Pfn4em1Hsc MGI:7428307


Genotype
MGI:7428307
hm1
Allelic
Composition
Pfn4em1Hsc/Pfn4em1Hsc
Genetic
Background
C57BL/6J-Pfn4em1Hsc
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pfn4em1Hsc mutation (0 available); any Pfn4 mutation (18 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• in male mice, absolute and relative weight of testes and epididymis are normal, overall cauda epididymis morphology is unaffected, seminiferous tubules show normal actin cytoskeleton organization, and testes show no evidence of male germ cell apoptosis or phagocytosis of germ cells by Sertoli cells
• female mice exhibit normal fertility
• impaired manchette development results in abnormal sperm flagellum structural defects
• cauda epididymal sperm show cytoplasmic droplets in the connecting piece as well as a bent connecting piece
• cauda epididymal sperm show cytoplasmic droplets in the midpiece, a bent midpiece, and an abnormally shortened thick midpiece
• cauda epididymal sperm show an abnormal fibrous sheath with mitochondrial structural defects
• eosin and nigrosine (E&N) staining of mature cauda epididymal sperm show an abnormally low % of viable sperm (25%) relative to heterozygous and wild-type control males (60-80%)
• hypo-osmotic swelling test (where tail curling = live sperm cells) show an abnormally low % of hypo-osmotic reactive sperm (24%) relative to control males
• 77% of mature cauda epididymal sperm display a severely disturbed, irregular/round head shape and smaller head size
• 16% of sperm exhibit a less aberrant head shape that is similar to that seen in control sperm
• abnormal acrosome biogenesis with fragmented Golgi network in spermatids
• mature sperm isolated from the cauda epididymis display malformed acrosomes
• acrosome biogenesis is impaired due to disruption of cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles
• round spermatids fail to properly fuse proacrosomal granules/vesicles to form the acrosome
• elongating spermatozoa exhibit smaller nuclei
• sperm nuclear area, perimeter, regularity, bounding width and circularity are significantly altered
• amorphous and smaller head shape
• elongating spermatozoa appear misshapen with apparently smaller nuclei
• step 11-13 spermatids lack the typical parallel microtubular array structure of the manchette and appear scraggy and rugged in shape
• step 12-16 spermatids show a complete loss of the manchette and amorphous head shape
• spermatids exhibit mis-localization (steps 8-9) and an angular shape (step 10) of the microtubular manchette
• in steps 11-13, spermatids completely lack the microtubular array structure
• manchette formation is disrupted leading to deformed sperm heads and flagellar defects
• however, perinuclear ring formation is not affected
• in some cases, the manchette appears to be absent
• CASA analysis revealed a significant reduction in total sperm motility
• curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP) and progressive motility are significantly reduced
• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes
• all adult males fail to produce pregnancy or offspring
• however, mating behavior is normal as vaginal plugs are clearly observed
• sperm are unable to fertilize wild-type oocytes with an intact zona pellucida in IVF assays
• however, when sperm are incubated with wild-type zona-free eggs, 30% of oocytes are successfully fertilized and develop to the morula/blastocyst stage
• in vitro, the rate of A23187-induced acrosome reaction is severely reduced, with only 5-6% of sperm exhibiting acrosome exocytosis versus 72% and 65% of sperm from wild-type and heterozygous controls, respectively

cellular
N
• testes exhibit no organizational defects in the actin cytoskeleton; no differences in male germ cell apoptosis are observed relative to controls
• impaired manchette development results in abnormal sperm flagellum structural defects
• cauda epididymal sperm show cytoplasmic droplets in the connecting piece as well as a bent connecting piece
• cauda epididymal sperm show cytoplasmic droplets in the midpiece, a bent midpiece, and an abnormally shortened thick midpiece
• cauda epididymal sperm show an abnormal fibrous sheath with mitochondrial structural defects
• eosin and nigrosine (E&N) staining of mature cauda epididymal sperm show an abnormally low % of viable sperm (25%) relative to heterozygous and wild-type control males (60-80%)
• hypo-osmotic swelling test (where tail curling = live sperm cells) show an abnormally low % of hypo-osmotic reactive sperm (24%) relative to control males
• 77% of mature cauda epididymal sperm display a severely disturbed, irregular/round head shape and smaller head size
• 16% of sperm exhibit a less aberrant head shape that is similar to that seen in control sperm
• abnormal acrosome biogenesis with fragmented Golgi network in spermatids
• mature sperm isolated from the cauda epididymis display malformed acrosomes
• acrosome biogenesis is impaired due to disruption of cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles
• round spermatids fail to properly fuse proacrosomal granules/vesicles to form the acrosome
• elongating spermatozoa exhibit smaller nuclei
• sperm nuclear area, perimeter, regularity, bounding width and circularity are significantly altered
• amorphous and smaller head shape
• elongating spermatozoa appear misshapen with apparently smaller nuclei
• step 11-13 spermatids lack the typical parallel microtubular array structure of the manchette and appear scraggy and rugged in shape
• step 12-16 spermatids show a complete loss of the manchette and amorphous head shape
• spermatids exhibit mis-localization (steps 8-9) and an angular shape (step 10) of the microtubular manchette
• in steps 11-13, spermatids completely lack the microtubular array structure
• manchette formation is disrupted leading to deformed sperm heads and flagellar defects
• however, perinuclear ring formation is not affected
• in some cases, the manchette appears to be absent
• spermatids display defective Golgi networks in testis sections: the cis-Golgi network is structurally disrupted and mildly mis-localized while the trans-Golgi network is fragmented and dispersed throughout the cytoplasm
• testicular protein levels of PI3K, AKT and mTOR are elevated whereas AMPK level is reduced, resulting in autophagy inhibition
• moreover, testicular protein levels of LC3BI/II (a marker for autophagy activation) and SQSTM1 (a marker for autophagic/lysosomal degradation) are increased, suggesting that accumulation of autophagosomes leads to blockage of the autophagic flux
• CASA analysis revealed a significant reduction in total sperm motility
• curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP) and progressive motility are significantly reduced
• spermatids display disorganization of the cis- and trans-Golgi networks, indicating impaired vesicle trafficking and transport
• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes

homeostasis/metabolism
• testicular protein levels of PI3K, AKT and mTOR are elevated whereas AMPK level is reduced, resulting in autophagy inhibition
• moreover, testicular protein levels of LC3BI/II (a marker for autophagy activation) and SQSTM1 (a marker for autophagic/lysosomal degradation) are increased, suggesting that accumulation of autophagosomes leads to blockage of the autophagic flux

endocrine/exocrine glands
• proteins involved in Golgi membrane trafficking and the PI3K/AKT pathway (ARF3, SPECC1L and FKBP1) are more abundant in the testes





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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
11/12/2024
MGI 6.24
The Jackson Laboratory