Phenotypes associated with this allele

• Allele Symbol: Actl7b^{tm1(KOMP)Vlcg}
• Allele Name: targeted mutation 1, Velocigene
• Allele ID: MGI:4399183
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Actl7b^tm1(KOMP)Vlcg/Actl7b^tm1(KOMP)Vlcg	C57BL/6N-Actl7b^tm1(KOMP)Vlcg	MGI:7488110

Genotype
MGI:7488110

hm1

• Allelic Composition: Actl7b^{tm1(KOMP)Vlcg}/Actl7b^{tm1(KOMP)Vlcg}
• Genetic Background: C57BL/6N-Actl7b^{tm1(KOMP)Vlcg}
• Cell Lines: 10808A-C2

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

reproductive system

oligozoospermia ( J:334022 )

♂ • cauda epididymal sperm counts are reduced 10-fold relative to wild-type controls

teratozoospermia ( J:334022 )

♂ • cauda epididymal sperm exhibit severe teratozoospermia with variable structural defects in the heads and flagella

♂ • detergent demembranated sperm show a range of ultrastructural anomalies, with most sperm showing major defects; least affected sperm exhibit a flagellar principal piece, occasional nuclear pore complexes (NPCs) and a roughly falciform shape, whereas severely affected sperm lack a sub-acrosomal region (SAR), an equatorial segment (ES), and a flagellar connecting piece

abnormal sperm flagellum morphology ( J:334022 )

♂ • multiple morphological abnormalities of the flagellum (MMAF) are observed

♂ • ~30% of sperm exhibit flagella wrapped around the head

abnormal outer dense fiber morphology ( J:334022 )

♂ • ODFs appear to dissociate not only from each other but also from the connecting piece (which is no longer detectable in epididymal sperm)

abnormal sperm connecting piece morphology ( J:334022 )

♂ • no flagellar connecting piece is identified in intact epididymal sperm

♂ • demembranated epididymal sperm show conspicuous absence of flagellar connecting pieces including the capitulum, segmented columns, and the nuclear-associated basal plate where the connecting piece attaches to the sperm flagellum

♂ • however, affected structures appear relatively normal in testicular sperm, suggesting that the integrity of the connecting piece is lost during epididymal transit

abnormal sperm midpiece morphology ( J:334022 )

♂ • flagellar midpiece segments are reduced in epididymal sperm; average length of the midpiece is 8.7 um versus 20.2 um in wild-type sperm

♂ • 25% of epididymal sperm lack the midpiece

♂ • SEM confirmed that the midpiece is absent in many sperm and thin and shortened in others

♂ • however, midpiece structures appear relatively normal in testicular sperm, suggesting that the integrity of the midpiece is lost during epididymal transit

abnormal sperm annulus morphology ( J:334022 )

♂ • SEM analysis of cauda epididymal sperm showed that the connection between the mitochondrial sheath and annulus is lost in some sperm

♂ • however, the principal piece region contains an axoneme with the typical 9 + 2 arrangement, ODFs, and fibrous sheath

abnormal sperm mitochondrial sheath morphology ( J:334022 )

♂ • SEM analysis of cauda epididymal sperm showed that the connection between the mitochondrial sheath and annulus is lost in some sperm

♂ • mitochondria are often clustered rather than forming the typical spiral pattern over the length of the midpiece; only 2.4% of sperm show normal mitochondrial distribution

♂ • sperm exhibit mitochondria in disorganized clumps on the midpiece (14.7%), in the midpiece plus head regions (6.6%), in the head region only (45.7%), or altogether absent (30.5%)

♂ • F-actin (a component of intermitochondrial cement) is weakly detectable in areas where mitochondria are indicated by brightfield morphology, but not in regions of sperm flagella where midpieces are bare/lack the mitochondrial sheath

absent sperm mitochondrial sheath ( J:334022 )

♂ • 30.5% of cauda epididymal sperm exhibit absent mitochondria

abnormal sperm head morphology ( J:334022 )

♂ • SEM confirmed that flagella are often wrapped around the sperm head

♂ • detergent demembranated sperm exhibit sub-membranous structures with aberrant fibers in the head region, not observed in intact sperm; aberrant fibers are composed of flagellar proteins

♂ • demembranated sperm show conspicuous absence of the sub-acrosomal region (SAR) and equatorial segment (ES) of the sperm head

♂ • cauda epididymal sperm exhibit mitochondria in disorganized clumps in the midpiece plus head regions (6.6%) or in the head region only (45.7%)

♂ • late-stage condensed spermatids show no aberrant fibers in the head region, suggesting that flagellar components in the head region appear during epididymal transit rather than initial mis-localization during flagellar development

abnormal sperm nucleus morphology ( J:334022 )

♂ • detergent demembranated sperm show nuclear shaping defects

increased male germ cell apoptosis ( J:334022 )

♂ • numerous TUNEL-positive cells, including many rounded cells, are detected in the epididymal lumina, unlike in wild-type controls

♂ • 60% of recognizable sperm (with flagella and DAPI-stained nuclei) are TUNEL-negative; when other cells (DAPI-stained nuclei but no flagella) are included, only ~28% of cells are TUNEL-negative

♂ • rounded TUNEL-positive cells are also noted near the luminal surface of seminiferous tubules, indicating that germ cell loss in the testis contributes to reduced epididymal sperm count

decreased sperm progressive motility ( J:334022 )

♂ • sperm lack apparent forward progressive motility

asthenozoospermia ( J:334022 )

♂ • less than 1% of sperm exhibit any detectable flagellar movement

abnormal seminiferous tubule epithelium morphology ( J:334022 )

♂ • some areas of the seminiferous epithelium appear disrupted, suggesting germ cell sloughing into the lumina

small testis ( J:334022 )

♂

decreased testis weight ( J:334022 )

♂ • testis weight is reduced by 20% relative to wild-type controls

♂ • however, whole body and other organ weights (including paired seminal vesicle weights) are relatively normal

abnormal spermiogenesis ( J:334022 )

♂

decreased epididymis weight ( J:334022 )

♂ • epididymis weight is reduced by 20% relative to wild-type controls

male infertility ( J:334022 )

♂ • all male homozygotes mated individually with two wild-type females for 2 months failed to sire offspring

cellular

oligozoospermia ( J:334022 )

♂ • cauda epididymal sperm counts are reduced 10-fold relative to wild-type controls

teratozoospermia ( J:334022 )

♂ • cauda epididymal sperm exhibit severe teratozoospermia with variable structural defects in the heads and flagella

♂ • detergent demembranated sperm show a range of ultrastructural anomalies, with most sperm showing major defects; least affected sperm exhibit a flagellar principal piece, occasional nuclear pore complexes (NPCs) and a roughly falciform shape, whereas severely affected sperm lack a sub-acrosomal region (SAR), an equatorial segment (ES), and a flagellar connecting piece

abnormal sperm flagellum morphology ( J:334022 )

♂ • multiple morphological abnormalities of the flagellum (MMAF) are observed

♂ • ~30% of sperm exhibit flagella wrapped around the head

abnormal outer dense fiber morphology ( J:334022 )

♂ • ODFs appear to dissociate not only from each other but also from the connecting piece (which is no longer detectable in epididymal sperm)

abnormal sperm connecting piece morphology ( J:334022 )

♂ • no flagellar connecting piece is identified in intact epididymal sperm

♂ • demembranated epididymal sperm show conspicuous absence of flagellar connecting pieces including the capitulum, segmented columns, and the nuclear-associated basal plate where the connecting piece attaches to the sperm flagellum

♂ • however, affected structures appear relatively normal in testicular sperm, suggesting that the integrity of the connecting piece is lost during epididymal transit

abnormal sperm midpiece morphology ( J:334022 )

♂ • flagellar midpiece segments are reduced in epididymal sperm; average length of the midpiece is 8.7 um versus 20.2 um in wild-type sperm

♂ • 25% of epididymal sperm lack the midpiece

♂ • SEM confirmed that the midpiece is absent in many sperm and thin and shortened in others

♂ • however, midpiece structures appear relatively normal in testicular sperm, suggesting that the integrity of the midpiece is lost during epididymal transit

abnormal sperm annulus morphology ( J:334022 )

♂ • SEM analysis of cauda epididymal sperm showed that the connection between the mitochondrial sheath and annulus is lost in some sperm

♂ • however, the principal piece region contains an axoneme with the typical 9 + 2 arrangement, ODFs, and fibrous sheath

abnormal sperm mitochondrial sheath morphology ( J:334022 )

♂ • SEM analysis of cauda epididymal sperm showed that the connection between the mitochondrial sheath and annulus is lost in some sperm

♂ • mitochondria are often clustered rather than forming the typical spiral pattern over the length of the midpiece; only 2.4% of sperm show normal mitochondrial distribution

♂ • sperm exhibit mitochondria in disorganized clumps on the midpiece (14.7%), in the midpiece plus head regions (6.6%), in the head region only (45.7%), or altogether absent (30.5%)

♂ • F-actin (a component of intermitochondrial cement) is weakly detectable in areas where mitochondria are indicated by brightfield morphology, but not in regions of sperm flagella where midpieces are bare/lack the mitochondrial sheath

absent sperm mitochondrial sheath ( J:334022 )

♂ • 30.5% of cauda epididymal sperm exhibit absent mitochondria

abnormal sperm head morphology ( J:334022 )

♂ • SEM confirmed that flagella are often wrapped around the sperm head

♂ • detergent demembranated sperm exhibit sub-membranous structures with aberrant fibers in the head region, not observed in intact sperm; aberrant fibers are composed of flagellar proteins

♂ • demembranated sperm show conspicuous absence of the sub-acrosomal region (SAR) and equatorial segment (ES) of the sperm head

♂ • cauda epididymal sperm exhibit mitochondria in disorganized clumps in the midpiece plus head regions (6.6%) or in the head region only (45.7%)

♂ • late-stage condensed spermatids show no aberrant fibers in the head region, suggesting that flagellar components in the head region appear during epididymal transit rather than initial mis-localization during flagellar development

abnormal sperm nucleus morphology ( J:334022 )

♂ • detergent demembranated sperm show nuclear shaping defects

increased male germ cell apoptosis ( J:334022 )

♂ • numerous TUNEL-positive cells, including many rounded cells, are detected in the epididymal lumina, unlike in wild-type controls

♂ • 60% of recognizable sperm (with flagella and DAPI-stained nuclei) are TUNEL-negative; when other cells (DAPI-stained nuclei but no flagella) are included, only ~28% of cells are TUNEL-negative

♂ • rounded TUNEL-positive cells are also noted near the luminal surface of seminiferous tubules, indicating that germ cell loss in the testis contributes to reduced epididymal sperm count

decreased sperm progressive motility ( J:334022 )

♂ • sperm lack apparent forward progressive motility

asthenozoospermia ( J:334022 )

♂ • less than 1% of sperm exhibit any detectable flagellar movement

endocrine/exocrine glands

abnormal seminiferous tubule epithelium morphology ( J:334022 )

♂ • some areas of the seminiferous epithelium appear disrupted, suggesting germ cell sloughing into the lumina

small testis ( J:334022 )

♂

decreased testis weight ( J:334022 )

♂ • testis weight is reduced by 20% relative to wild-type controls

♂ • however, whole body and other organ weights (including paired seminal vesicle weights) are relatively normal