Analysis Tools
mortality/aging
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• no homozygotes are recovered from multiple breeding pairs; no signs of fetal resorption are detected in timed matings, suggesting early embryonic lethality
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Allele Symbol Allele Name Allele ID |
Tmem258tm1.1(KOMP)Vlcg targeted mutation 1.1, Velocigene MGI:5892142 |
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| Summary |
3 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no homozygotes are recovered from multiple breeding pairs; no signs of fetal resorption are detected in timed matings, suggesting early embryonic lethality
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• DSS-treated heterozygotes exhibit a higher frequency of apoptotic colonic epithelial cells than DSS-treated wild-type controls, as shown by active caspase 3 staining
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• DSS-treated heterozygotes exhibit decreased proliferation and disorganized dispersion of colonic epithelial cells relative to DSS-treated wild-type controls, as shown by Ki67 staining
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• DSS-treated heterozygotes show more severe colonic crypt destruction than DSS-treated wild-type controls
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• DSS-treated heterozygotes show reduced colon length relative to DSS-treated wild-type controls
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• at day 8 after oral administration of 2.5% dextran sulfate sodium (DSS), heterozygotes show accelerated weight loss, increased histopathological severity scores (based on severity of inflammation, depth of inflammation and crypt damage), decreased colon length, reduced epithelial proliferation in response to injury, and a marked inflammatory gene expression signature in colonic tissue relative to wild-type controls
• however, untreated heterozygotes exhibit normal intestinal barrier function
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• following oral administration of 2.5% DSS for 7 days, heterozygotes show accelerated mortality with a >75% decline in survival at 10 and 15 days post-treatment, unlike in wild-type controls where a ~40% decline in survival does not occur until 15 days post-treatment
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• DSS-treated heterozygotes show accelerated weight loss relative to DSS-treated wild-type controls
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• at day 8 after oral administration of 2.5% dextran sulfate sodium (DSS), heterozygotes show accelerated weight loss, increased histopathological severity scores (based on severity of inflammation, depth of inflammation and crypt damage), decreased colon length, reduced epithelial proliferation in response to injury, and a marked inflammatory gene expression signature in colonic tissue relative to wild-type controls
• however, untreated heterozygotes exhibit normal intestinal barrier function
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• following oral administration of 2.5% DSS for 7 days, heterozygotes show accelerated mortality with a >75% decline in survival at 10 and 15 days post-treatment, unlike in wild-type controls where a ~40% decline in survival does not occur until 15 days post-treatment
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• DSS-treated heterozygotes show more severe colonic crypt destruction than DSS-treated wild-type controls
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• DSS-treated heterozygotes exhibit a higher frequency of apoptotic colonic epithelial cells than DSS-treated wild-type controls, as shown by active caspase 3 staining
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• DSS-treated heterozygotes exhibit decreased proliferation and disorganized dispersion of colonic epithelial cells relative to DSS-treated wild-type controls, as shown by Ki67 staining
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• after induction of colitis with DSS, heterozygotes show clear evidence of ER stress in the colonic epithelium, with an increased frequency of HSPA5 (BiP/GRP78)-positive epithelial cells relative to wild-type controls
• however, untreated heterozygotes do not exhibit significant ER stress in colonic epithelium
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• following oral administration of 2.5% DSS for 7 days, heterozygotes show accelerated mortality with a >75% decline in survival at 10 and 15 days post-treatment, unlike in wild-type controls where a ~40% decline in survival does not occur until 15 days post-treatment
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• after introduction of single guide RNAs (sgRNAs) targeting exonic Tmem258 sequences (Tmem258 CRISPR) by transduction with lentiviral particles co-encoding Cre recombinase, spheroid cultures derived from colonic crypts exhibit fewer viable Cas9-GFP-positive cells than colonic organoid cultures that have received control sgRNAs targeting noncoding intronic Tmem258 regions
• morphologically, Tmem258 CRISPR organoids contain scattered Cas9-GFP-positive cells within small spheroids that encapsulate numerous dead cells within the lumen, whereas control CRISPR organoids appear healthier and larger with contiguous Cas9-GFP-positive cells suggestive of active proliferation
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• after simultaneous delivery of Cre recombinase and sgRNA targeting of Tmem258 sequences by lentiviral transduction, Tmem258 CRISPR organoid cultures contain more in-frame mutations in Cas9-GFP-positive cells than control CRISPR organoids, suggesting that out-of-frame alleles are negatively selected, consistent with increased ER stress
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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 05/07/2024 MGI 6.23 |
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