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Allele Symbol Allele Name Allele ID |
Casp9tm1Flv targeted mutation 1, Richard A Flavell MGI:2158755 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in 2 homozygotes that survived to at least 6 weeks of age, injection with anti-Fas antibody Jo2 caused death, as seen in wildtype mice, but at 6 hours which is a delay in timeline, and the apoptotic pathway aberrently involves activation, but not altered expression, of caspases 2, 6, and 7
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• normal mendelian ratio at E16.5 but fewer than 3% of the pups born are homozygotes
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• absence of activated caspase 3 in the developing brain as assessed by immunohistochemistry with antibody CM1
(J:49088)
• nearly 10 fold reduction in TUNEL-positive cells in E12.5 neuroepithelium
(J:49088)
• fewer TUNEL-positive cells in the E16.5 spinal cord and E12.5 dorsal root ganglia although there is no change in TUNEL staining in E12.5 liver
(J:49088)
• E13 olfactory epithelium has lower levels of olfactory receptor neuron apoptosis than normal
(J:90572)
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• lamina terminalis of the forebrain is thicker with increased number and density of cells
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• at E13.5, the hindbrain neural tube remains open
• failure of neural tube closure in hindbrain region apparent by E10.5
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• enlargement of the proliferative zone in the forebrain and midbrain with resultant protrusion of brain mass
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• lacking pyknotic clusters at E10.5 unlike in heterozygous controls
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• E16.5 expanded midbrain displaces telencephalic vesicles
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• at E10.5 and E13.5, a defect at the midbrain/hindbrain junction is observed
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• notable expansion in the the midbrain region underneath the fetal skin tissue at E13.5
• by E16.5, expanded midbrain protrudes and displaces the telencephalic vesicles
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• third ventricles obstructed by E13.5
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• stenosis of the cerebral ventricles
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• heterotopias and discontinuities of the proliferative ventricular zone lead to invagination and complete interruption of the telencephalic wall
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• lateral ventricles obstructed by E13.5
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• by E16.5 prominent exencephaly of the entire cranial tissues with enlarged and irregularly shaped protruding brain masses
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| N |
• normal apoptosis in interdigital webbing retraction
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• 5 Gy gamma-irradiation of CD4+CD8+ thymocytes from hosts reconstituted with Casp9tm1Flv homozygous fetal liver do not display caspase 2 cleavage while those derived from wildtype fetal liver do
(J:103480)
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• thymocytes are delayed in apoptotic response to anti-CD3 + andi-CD28, etoposide, gamma irradiation, and dexamethasone, but have normal apoptotic response to Fas stimulation
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• a slight resistance to apoptosis is found in thymocytes treated with gamma-irradiation, dexamethasone, PMA, or etoposide and in embryonic fibroblasts treated with etoposide
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• absence of activated caspase 3 in the developing brain as assessed by immunohistochemistry with antibody CM1
(J:49088)
• nearly 10 fold reduction in TUNEL-positive cells in E12.5 neuroepithelium
(J:49088)
• fewer TUNEL-positive cells in the E16.5 spinal cord and E12.5 dorsal root ganglia although there is no change in TUNEL staining in E12.5 liver
(J:49088)
• E13 olfactory epithelium has lower levels of olfactory receptor neuron apoptosis than normal
(J:90572)
|
| N |
• normal spinal cord, heart, and lung morphology at E16.5
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• lacking pyknotic clusters at E10.5 unlike in heterozygous controls
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• lamina terminalis of the forebrain is thicker with increased number and density of cells
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• failure of neural tube closure in hindbrain region apparent by E10.5
• at E13.5, the hindbrain neural tube remains open
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| N |
• normal thymic size, cellularity, and proportions of CD4 and CD8
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• thymocytes are delayed in apoptotic response to anti-CD3 + andi-CD28, etoposide, gamma irradiation, and dexamethasone, but have normal apoptotic response to Fas stimulation
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• a slight resistance to apoptosis is found in thymocytes treated with gamma-irradiation, dexamethasone, PMA, or etoposide and in embryonic fibroblasts treated with etoposide
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• E13 olfactory epithelium neuronal layer is thicker than normal
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• E13 olfactory epithelium neuronal layer is thicker than normal
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• E13 olfactory epithelium neuronal layer is thicker than normal
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| N |
• wildtype irradiated hosts reconstituted with E14.5 Casp2 heterozygous or wildtype Casp9tm1Flv homozygous fetal liver develop nomral thymocyte numbers and sub-populations with no thymocyte upregulation of caspases 1, 3, 6, 7, 8, or 9, normal B cell and T cell apoptosis in response to cytokine withdrawal, and normal T cell sensitivity to dexamethasone
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• thymocytes are delayed in apoptotic response to anti-CD3 + andi-CD28, etoposide, gamma irradiation, and dexamethasone, but have normal apoptotic response to Fas stimulation
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• a slight resistance to apoptosis is found in thymocytes treated with gamma-irradiation, dexamethasone, PMA, or etoposide and in embryonic fibroblasts treated with etoposide
|
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• thymocytes are delayed in apoptotic response to anti-CD3 + andi-CD28, etoposide, gamma irradiation, and dexamethasone, but have normal apoptotic response to Fas stimulation
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• E13 olfactory epithelium neuronal layer is thicker than normal
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E12.5 brainstem and dorsal root ganglia do not have the apoptosis found in Bcl2tm1Dlo homozygotes, and E12.5 primary telencephalic cultures show decreased cell death and no caspase 3 activation relative to those of Bcl2l1tm1Dlo homozygotes
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• E12.5 liver has increased apoptosis similar to that seen in Bcl2l1tm1Dlo homozygotes indicating no requirement for caspase 9 in liver apoptotis
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• E12.5 histology shows thickened telencephalic vesicle, expanded ventricular zones, and cortical dysplasia
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• E12.5 brainstem and dorsal root ganglia, show increased numbers of apoptotic cells, and E12.5 primary telencephalic cultures show increased caspase 3 activation and cell death
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• E12.5 liver show increased apoptotic cells
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• E12.5 brainstem and dorsal root ganglia, show increased numbers of apoptotic cells, and E12.5 primary telencephalic cultures show increased caspase 3 activation and cell death
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at E14.5 a majority of embryos display brain over-growth similar to that found in Casp9tm1Flv homozygotes
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• thymocytes grown in wildtype hosts have only 10-20% of the DEVD-ase activity of wildtype or thymocytes deficient for only caspase 2
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| N |
• irradiated wildtype hosts reconstituted with E14.5 Casp2tm1Vaux Casp9tm1Flv double homozygous fetal liver develop normal thymocyte numbers and sub-populations with no thymocyte upregulation of caspases 1, 3, 6, 7, 8, or 9, normal B cell and T cell apoptosis in response to cytokine withdrawal, and normal T cell sensitivity to dexamethasone
• dexamethasone induced apoptosis of T cells (grown in wildtype hosts from E14.5 fetal liver) is blocked by caspase inhibitors but not by calpain and cathepsin inhibitors
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• thymocytes grown in wildtype hosts have only 10-20% of the DEVD-ase activity of wildtype or thymocytes deficient for only caspase 2
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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 07/05/2024 MGI 6.24 |
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