Analysis Tools|
Allele Symbol Allele Name Allele ID |
Gpx4tm1Yana targeted mutation 1, Yasuhito Nakagawa MGI:2663628 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• embryos die between E7.5 and E8.5
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• increased apoptosis relative to wild-type at E7.5
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• lipid peroxidation is increased in inner segment photoreceptor cells at P12, and a modest increase is seen in the other layers of the retina including the inner nuclear layer and ganglion cell layer
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• 80% decrease in the number of connecting cilia in photoreceptor cells
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• mitochondrial area in inner segment of photoreceptor cells is decreased indicating a decrease in mitochondrial biomass at P11
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• the outer segment layer is very thin
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• the outer segment is disorganized and consists of cell membranes that branch and form a large web-like network structure without apparent disc rim and an abnormally wide intra- and inter-outer segment membrane space
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• milder thinning or degeneration of the inner nuclear layer
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• rapid loss of the outer nuclear layer
• an increasing number of TUNEL+ cells are seen in the outer nuclear layer after P12
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• mice show rapid and massive retinal degeneration after P12 with none of the photoreceptor cells retained by P21
• cone photoreceptor cells are lost earlier than rod photoreceptor cells
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• 80% decrease in the number of connecting cilia in photoreceptor cells
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• mitochondrial area in inner segment of photoreceptor cells is decreased indicating a decrease in mitochondrial biomass at P11
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• the outer segment layer is very thin
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• the outer segment is disorganized and consists of cell membranes that branch and form a large web-like network structure without apparent disc rim and an abnormally wide intra- and inter-outer segment membrane space
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• 80% decrease in the number of connecting cilia in photoreceptor cells
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• mitochondrial DNA replication in the whole retina is lower
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 9 week old mice show a decrease in total body weight
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• mice show an increase in diploid germ cells whereas cells with haploid DNA content are reduced
• elevation of intracellular hydroperoxide in germ cells
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• the internal membrane structure of the spermatozoa mitochondria is irregular, with disappearance of cristae-like folds and formation of electron-dense central clumps
• however, the outer mitochondrial membranes are normal
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• epididymal spermatozoa exhibit severe flagellar defects, with flagellum folded at the midpiece-principal junction into a sharp hairpin configuration
• testicular spermatozoa are fully formed and have extended flagellum, however caput spermatozoa show abnormal flagellar bending in the posterior midpiece of the flagellum
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• in 70% of seminiferous tubules, little or no spermatocytes, spermatids, or sperm are seen
• only spermatogonia are seen among germinal cells in damaged seminiferous tubules, indicating that germinal cells die before postnatal mitosis but not before meiosis
• mice show more seminiferous tubules with activated caspase 3+ spermatocytes, indicating germ cell death
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• spermatozoa number in epididymal semen is decreased
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• males are infertile
• spermatozoa show no evidence of fertilization of wild-type eggs in vitro
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• mitochondrial membrane potential of cauda spermatozoa is decreased after 2 hours in vitro incubation in TYH medium but is normally maintained when in vitro incubation is omitted
• mitochondria of cauda spermatozoa show a reduction in the active respiration state and a decrease in the respiratory efficiency
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• forward motility of spermatozoa is reduced to 24% of controls
• hairpin configuration spermatozoa frequently show weak flagellar beating particularly at the principal segment
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• mice show an increase in diploid germ cells whereas cells with haploid DNA content are reduced
• elevation of intracellular hydroperoxide in germ cells
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• the internal membrane structure of the spermatozoa mitochondria is irregular, with disappearance of cristae-like folds and formation of electron-dense central clumps
• however, the outer mitochondrial membranes are normal
|
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|
• epididymal spermatozoa exhibit severe flagellar defects, with flagellum folded at the midpiece-principal junction into a sharp hairpin configuration
• testicular spermatozoa are fully formed and have extended flagellum, however caput spermatozoa show abnormal flagellar bending in the posterior midpiece of the flagellum
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• in 70% of seminiferous tubules, little or no spermatocytes, spermatids, or sperm are seen
• only spermatogonia are seen among germinal cells in damaged seminiferous tubules, indicating that germinal cells die before postnatal mitosis but not before meiosis
• mice show more seminiferous tubules with activated caspase 3+ spermatocytes, indicating germ cell death
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• spermatozoa number in epididymal semen is decreased
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• the internal membrane structure of the spermatozoa mitochondria is irregular, with disappearance of cristae-like folds and formation of electron-dense central clumps
• however, the outer mitochondrial membranes are normal
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|
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• forward motility of spermatozoa is reduced to 24% of controls
• hairpin configuration spermatozoa frequently show weak flagellar beating particularly at the principal segment
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• mitochondrial membrane potential of cauda spermatozoa is decreased after 2 hours in vitro incubation in TYH medium but is normally maintained when in vitro incubation is omitted
• mitochondria of cauda spermatozoa show a reduction in the active respiration state and a decrease in the respiratory efficiency
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice are viable and fertile and live for at least more than 1 year, indicating rescue of the embryonic lethality seen in Gpx4 knock-out mice
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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 11/19/2024 MGI 6.24 |
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