Analysis Tools|
Allele Symbol Allele Name Allele ID |
Notch1tm1Agt targeted mutation 1, Michael Aguet MGI:1933835 |
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
18 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• embryos start to die shortly after E13.5
|
|
• compact myocardium thickness is signficantly reduced in mutants
• number of nuclei is lower (25-30%) at E13.5, with reduction in proliferating cells observed compared to control
|
|
• reduction in number of smooth muscle cells in the compact myocardium is observed at E13.5
|
|
• at E13.5 hearts exhibit severe reduction and disorganization of the coronary vascular plexus
• abnormal development of CVs is associated with endocardial-subepicardial connections that result in cysts with endothelial lining connected to the outer ventricular myocardium
|
|
• coronary arteries are absent from the compact vemtricular myocardium, specifically the deep myocardium; coronary veins occupy a larger area of the subepicardium
|
|
• at E13.5 most embryos display body hemorrhages and die shortly afterwards
|
|
• at E13.5 most embryos display pericardial hemorrhages and die shortly afterwards
|
|
• at E13.5 most embryos display pericardial hemorrhages and die shortly afterwards
|
|
• compact myocardium thickness is signficantly reduced in mutants
• number of nuclei is lower (25-30%) at E13.5, with reduction in proliferating cells observed compared to control
|
|
• reduction in number of smooth muscle cells in the compact myocardium is observed at E13.5
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• arrested
|
|
• at E10.5, atrioventricular cushions exhibit rounded endocardial-derived cells that accumulate at the cushion interface and less dense, hypoplastic areas unlike in control mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• irradiated wild-type mice reconstituted with Notch1/2-null bone marrow progenitors analyzed at 8 weeks show block at earliest intrathymic precursor stage; immature B cells develop in the thymus recapitulating the Notch1-null phenotype
• cultured double-null hematopoietic stem cells, HSCs do not develop into T cell progenitors after 10 days
|
|
• cultured double null HSCs display a block at the double negative 1 stage
|
|
• irradiated wild-type mice reconstituted with Notch1/2-null bone marrow progenitors analyzed at 8 weeks show block at earliest intrathymic precursor stage; immature B cells develop in the thymus recapitulating the Notch1-null phenotype
• cultured double-null hematopoietic stem cells, HSCs do not develop into T cell progenitors after 10 days
|
|
• cultured double null HSCs display a block at the double negative 1 stage
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at 8 weeks, dispersed gray hairs are observed
|
|
• at 8 weeks, dispersed gray hairs are observed
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• pigmentation mediated by non-follicular melanocytes such as in the ear or eye is not affected by this mutation
|
|
• when crossed to transgenic mice to visualize melanoblasts and melanocytes (dopachrome tautomerase - LacZ mice), at 9 days of age, a decreased number of melanocytes in the lower permanent portion of the hair follicle is observed; differences are greater at 3 and 4.5 weeks with most follicles lacking melanocytes
• mutant hair bulbs lack pigment after their first regeneration
|
|
• coat is completetly gray with coat slightly lighter in color compared to mice missing both Notch2 alleles and one Notch1 allele
• dilution is progressive and increases with age; there is an increasing number of gray and white hairs with age such that at 7 days coat color is indistinguishable from controls, but at 7 months, coat is completely white
|
|
• when crossed to transgenic mice to visualize melanoblasts and melanocytes (dopachrome tautomerase - LacZ mice), at 9 days of age, a decreased number of melanocytes in the lower permanent portion of the hair follicle is observed; differences are greater at 3 and 4.5 weeks with most follicles lacking melanocytes
• mutant hair bulbs lack pigment after their first regeneration
|
|
• coat is completetly gray with coat slightly lighter in color compared to mice missing both Notch2 alleles and one Notch1 allele
• dilution is progressive and increases with age; there is an increasing number of gray and white hairs with age such that at 7 days coat color is indistinguishable from controls, but at 7 months, coat is completely white
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• hair pigmentation is even more reduced with complete absence of Notch1 and 2 in melanocytes: hair is almost white
|
|
• hair pigmentation is even more reduced with complete absence of Notch1 and 2 in melanocytes: hair is almost white
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• dispersed gray hairs are observed, identical to Notch2 mutants or Notch1/Notch2 double heterozygotes, but first gray hairs are only visible at 12 weeks
|
|
• dispersed gray hairs are observed, identical to Notch2 mutants or Notch1/Notch2 double heterozygotes, but first gray hairs are only visible at 12 weeks
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• at E14.5, the acinar compartment is reduced compared to in wild-type mice
|
|
• at E14.5, the acinar compartment is reduced compared to in wild-type mice
|
|
• the endocrine epithelium is mildly disrupted
• however, morphology of the islets is normal
|
|
• the number of islets is decreased compared to in wild-type mice
|
|
• mice exhibit a 25% decrease in the number of proliferating cells compared to in wild-type mice
|
|
• at E13.5, pancreatic buds are less branched than in wild-type mice
|
|
• at E13.5, pancreatic buds are smaller than controls
|
|
• the pancreas is slightly smaller than in wild-type mice at P1
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die at around E10.5
|
|
• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning
|
|
• blood vessels fail to invade the placental labyrinth
|
|
• seen in some embryos
|
|
• at E9.5, embryos display growth arrest at the 16-to 20-somite stage
|
|
• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning
|
|
• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei
|
|
• somites are poorly defined, with signs of apoptosis
|
|
• embryos fail to remodel the primary vascular plexus to form large and small blood vessels of the mature yolk sac
|
|
• intersomitic blood vessels are poorly defined, with signs of apoptosis
|
|
• blood vessels fail to invade the placental labyrinth
|
|
• exhibit a marked reduction in vessel organization and a persistent, immature vascular plexus, suggesting a block in vascular maturation and angiogenic remodeling
• intact vasculogenesis but impaired secondary angiogenic sprouting and remodeling
|
|
• embryos show a decreased number of branching blood vessels throughout the embryo
|
|
• the anterior cardinal vein appears hypoplastic
|
|
• the heart displays delayed looping beginning at E9.5
|
|
• pericardial effusion is seen at E9.5 but not earlier
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium and tails
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium
|
|
• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei
|
|
• widespread apoptosis in neural cells and the inner endothelial lining of the aorta
|
|
• pericardial effusion is seen at E9.5 but not earlier
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• thymus cellularity is reduced 65% compared to age-matched controls
|
|
• some CD19lo thymic B cells have recombined Tcrb Dbeta1-Jbeta1 gene segments
|
|
• the percentage of thymocytes in the DN stages of T cell development are reduced compared to controls
• the percentage of thymocytes in the DN1 stage is reduced by a third with most of the reduction occurring at the DN1a and DN1b sub-stages
• the percentage of thymocytes in the DN2-DN3 stages are reduced by about 50% compared to controls
|
|
• double positive thymocytes make up just 65% of total thymocyte population compared to 80% in controls
|
|
• percentages of single-positive cells are increased in the thymus compared to controls
|
|
• 10-fold more B cells are found in the thymus compared to controls
• these B cells consist of a major CD19hi population and a minor CD19lo population with similar populations found in the bone marrow
• the CD19hi B cell population expresses cell surface markers similar to mature B2 B cells
• the CD19loB cell population have cell surface markers of pro- and pre- B cells
• single cell genotyping reveals about 94% of the CD19lo population has cre-mediated deletion of the floxed allele while only 26% of the CD19hi allele had the flox allele deleted
|
|
• the presence of recombined Tcrb gene segments in the abnormal CD19lo thymic B cells population suggests that the B cells differentiate from a DN1 T cell precursor
|
|
• thymus cellularity is reduced 65% compared to age-matched controls
|
|
• some CD19lo thymic B cells have recombined Tcrb Dbeta1-Jbeta1 gene segments
|
|
• the percentage of thymocytes in the DN stages of T cell development are reduced compared to controls
• the percentage of thymocytes in the DN1 stage is reduced by a third with most of the reduction occurring at the DN1a and DN1b sub-stages
• the percentage of thymocytes in the DN2-DN3 stages are reduced by about 50% compared to controls
|
|
• double positive thymocytes make up just 65% of total thymocyte population compared to 80% in controls
|
|
• percentages of single-positive cells are increased in the thymus compared to controls
|
|
• 10-fold more B cells are found in the thymus compared to controls
• these B cells consist of a major CD19hi population and a minor CD19lo population with similar populations found in the bone marrow
• the CD19hi B cell population expresses cell surface markers similar to mature B2 B cells
• the CD19loB cell population have cell surface markers of pro- and pre- B cells
• single cell genotyping reveals about 94% of the CD19lo population has cre-mediated deletion of the floxed allele while only 26% of the CD19hi allele had the flox allele deleted
|
|
• the presence of recombined Tcrb gene segments in the abnormal CD19lo thymic B cells population suggests that the B cells differentiate from a DN1 T cell precursor
|
|
• thymus cellularity is reduced 65% compared to age-matched controls
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• cell-fate mapping experiments suggest that some thymic dendritic cells are derived from DN1 T cell precursors
|
|
• recombined Tcrb Dbeta1-Jbeta1 gene segments are detectable in some thymic plasmacytoid dendritic cells and lymphoid dendritic cells
|
|
• cell-fate mapping experiments suggest that some thymic dendritic cells are derived from DN1 T cell precursors
|
|
• recombined Tcrb Dbeta1-Jbeta1 gene segments are detectable in some thymic plasmacytoid dendritic cells and lymphoid dendritic cells
|
|
• cell-fate mapping experiments suggest that some thymic dendritic cells are derived from DN1 T cell precursors
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• homozygous mutant mice exhibit normal hematopoiesis, including normal hematopoietic stem cell self-renewal and differentiation
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• some mutants injected with interferon-alpha at days 3, 6, 9, and 11 after birth to induce partial gene disruption die for unknown reasons
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show reduced body weight after two weeks post injection
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show transient growth retardation
|
|
• thymus architecture is abnormal in mutants injected with interferon-alpha to induce partial gene disruption, such that medullary and cortical regions cannot be distinguished
thymic dentritic cells are reduced
|
|
• mutants injected with interferon-alpha exhibit an accumulation of B cells in the thymus that differ from normally occurring thymic B cells and resemble immature B cells normally found in the bone marrow
(J:55400)
• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in Dll4tm1Frad homozygous control mice
(J:143472)
|
|
• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number
|
|
• hematopoietic stem cells do not develop in to B cells after 18 days in culture
|
|
• the absolute numbers of immature B cells in the thymus are increased 30-fold compared to in Dll4tm1Frad homozygous control mice
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show abnormal T cell maturation and show a block at or before the most immature T cell stage, as most triple-negative (CD4-CD8-TCR-) thymoctyes are CD44+CD25-
(J:55400)
• irradiated wild-type mice reconstituted with Notch1-null bone marrow progenitors analyzed at 8 weeks show block at earliest intrathymic precursor stage; immature B cells develop in the thymus
(J:125373)
• >90% of Notch1-null HSCs cultured on stromal cells for 28 days are blocked in the double negative compartment and do not progress from double negative to double positive
(J:125373)
|
|
• TCRgamma/delta+ double-negative thymocytes from mutants injected with interferon-alpha are decreased 10-fold
|
|
• thymocytes from mutants injected with interferon-alpha show a 9-fold reduction in double-positive cells
|
|
• thymocytes from mutants injected with interferon-alpha show a 5-fold reduction in CD4+ single-positive cells
|
|
• thymocytes from mutants injected with interferon-alpha show a 4.4-fold reduction in CD8+ single-positive cells
|
|
• immature single-positive thymocytes from mutants injected with interferon-alpha are decreased 13-fold
|
| N |
• mutants exhibit normal hematopoietic stem cell self-renewal and differentiation
|
|
• thymus architecture is abnormal in mutants injected with interferon-alpha to induce partial gene disruption, such that medullary and cortical regions cannot be distinguished
thymic dentritic cells are reduced
|
|
• mutants injected with interferon-alpha exhibit an accumulation of B cells in the thymus that differ from normally occurring thymic B cells and resemble immature B cells normally found in the bone marrow
(J:55400)
• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in Dll4tm1Frad homozygous control mice
(J:143472)
|
|
• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number
|
|
• hematopoietic stem cells do not develop in to B cells after 18 days in culture
|
|
• the absolute numbers of immature B cells in the thymus are increased 30-fold compared to in Dll4tm1Frad homozygous control mice
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show abnormal T cell maturation and show a block at or before the most immature T cell stage, as most triple-negative (CD4-CD8-TCR-) thymoctyes are CD44+CD25-
(J:55400)
• irradiated wild-type mice reconstituted with Notch1-null bone marrow progenitors analyzed at 8 weeks show block at earliest intrathymic precursor stage; immature B cells develop in the thymus
(J:125373)
• >90% of Notch1-null HSCs cultured on stromal cells for 28 days are blocked in the double negative compartment and do not progress from double negative to double positive
(J:125373)
|
|
• TCRgamma/delta+ double-negative thymocytes from mutants injected with interferon-alpha are decreased 10-fold
|
|
• thymocytes from mutants injected with interferon-alpha show a 9-fold reduction in double-positive cells
|
|
• thymocytes from mutants injected with interferon-alpha show a 5-fold reduction in CD4+ single-positive cells
|
|
• thymocytes from mutants injected with interferon-alpha show a 4.4-fold reduction in CD8+ single-positive cells
|
|
• immature single-positive thymocytes from mutants injected with interferon-alpha are decreased 13-fold
|
|
• thymus architecture is abnormal in mutants injected with interferon-alpha to induce partial gene disruption, such that medullary and cortical regions cannot be distinguished
thymic dentritic cells are reduced
|
|
• mutants injected with interferon-alpha exhibit an accumulation of B cells in the thymus that differ from normally occurring thymic B cells and resemble immature B cells normally found in the bone marrow
(J:55400)
• more thymic B cells are present than in control mice and they exhibit varying expression levels of IgM and B220 unlike in Dll4tm1Frad homozygous control mice
(J:143472)
|
|
• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus
|
|
• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the number of Map+ cells that differentiate in culture is increased while the number of Nes+ cells is decreased compared to in cultures from wild-type mice
|
|
• the number of Map+ cells that differentiate in culture is increased while the number of Nes+ cells is decreased compared to in cultures from wild-type mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• die at around E10.5
|
|
• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning
|
|
• blood vessels fail to invade the placental labyrinth
|
|
• seen in some embryos
|
|
• at E9.5, embryos display growth arrest at the 16-to 20-somite stage
|
|
• embryos show a pronounced delay in posterior development, with some showing incomplete embryonic turning
|
|
• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei
|
|
• somites are poorly defined, with signs of apoptosis
|
|
• embryos fail to remodel the primary vascular plexus to form large and small blood vessels of the mature yolk sac
|
|
• intersomitic blood vessels are poorly defined, with signs of apoptosis
|
|
• blood vessels fail to invade the placental labyrinth
|
|
• exhibit a marked reduction in vessel organization and a persistent, immature vascular plexus, suggesting a block in vascular maturation and angiogenic remodeling
• intact vasculogenesis but impaired secondary angiogenic sprouting and remodeling
|
|
• embryos show a decreased number of branching blood vessels throughout the embryo
|
|
• the anterior cardinal vein appears hypoplastic
|
|
• the heart displays delayed looping beginning at E9.5
|
|
• pericardial effusion is seen at E9.5 but not earlier
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium and tails
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium
|
|
• widespread apoptosis in neural cells and the inner endothelial lining of the aorta
|
|
• the forebrain neural tube is degenerated, with abundant pyknotic and fragmented nuclei
|
|
• pericardial effusion is seen at E9.5 but not earlier
|
|
• starting at E9.5, there is intraembryonic hemorrhage into the pericardium
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• the immune response to strong T helper2 inducing conditions is absent
|
|
• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells
|
|
• after 5 days of culture of antigen presenting cells with Schistosoma mansoni soluble egg antigen and pigeon cytochrome C, no IL-4 is produced as it is in wild-type cells
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• pigmentation mediated by non-follicular melanocytes such as in the ear or eye is not affected by this mutation
|
|
• coat is completetly gray
|
|
• coat is completetly gray
|
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 11/12/2024 MGI 6.24 |
|
|
|
||
