Phenotypes Associated with This Genotype

Genotype
MGI:2448711

• Allelic Composition: Notch1^tm1Agt/Notch1^tm1Agt; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129 * C57BL/6 * CBA

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

mortality/aging

premature death ( J:55400 )

• some mutants injected with interferon-alpha at days 3, 6, 9, and 11 after birth to induce partial gene disruption die for unknown reasons

growth/size/body

decreased body weight ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption show reduced body weight after two weeks post injection

postnatal growth retardation ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption show transient growth retardation

immune system

abnormal thymus morphology ( J:55400 )

• 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

abnormal thymus cell ratio ( J:55400 , J:143472 )

• 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 Dll4^tm1Frad homozygous control mice (J:143472)

small thymus ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus

decreased thymocyte number ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number

abnormal B cell differentiation ( J:125373 )

• hematopoietic stem cells do not develop in to B cells after 18 days in culture

increased immature B cell number ( J:143472 )

• the absolute numbers of immature B cells in the thymus are increased 30-fold compared to in Dll4^tm1Frad homozygous control mice

abnormal T cell differentiation ( J:55400 , J:125373 )

• 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)

decreased double-negative T cell number ( J:55400 )

• TCRgamma/delta+ double-negative thymocytes from mutants injected with interferon-alpha are decreased 10-fold

decreased double-positive T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 9-fold reduction in double-positive cells

decreased CD4-positive, alpha-beta T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 5-fold reduction in CD4+ single-positive cells

decreased CD8-positive, alpha-beta T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 4.4-fold reduction in CD8+ single-positive cells

decreased single-positive T cell number ( J:55400 )

• immature single-positive thymocytes from mutants injected with interferon-alpha are decreased 13-fold

hematopoietic system

hematopoietic system phenotype ( J:98129 )

N • mutants exhibit normal hematopoietic stem cell self-renewal and differentiation

abnormal thymus morphology ( J:55400 )

• 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

abnormal thymus cell ratio ( J:55400 , J:143472 )

• 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 Dll4^tm1Frad homozygous control mice (J:143472)

small thymus ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus

decreased thymocyte number ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number

abnormal B cell differentiation ( J:125373 )

• hematopoietic stem cells do not develop in to B cells after 18 days in culture

increased immature B cell number ( J:143472 )

• the absolute numbers of immature B cells in the thymus are increased 30-fold compared to in Dll4^tm1Frad homozygous control mice

abnormal T cell differentiation ( J:55400 , J:125373 )

• 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)

decreased double-negative T cell number ( J:55400 )

• TCRgamma/delta+ double-negative thymocytes from mutants injected with interferon-alpha are decreased 10-fold

decreased double-positive T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 9-fold reduction in double-positive cells

decreased CD4-positive, alpha-beta T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 5-fold reduction in CD4+ single-positive cells

decreased CD8-positive, alpha-beta T cell number ( J:55400 )

• thymocytes from mutants injected with interferon-alpha show a 4.4-fold reduction in CD8+ single-positive cells

decreased single-positive T cell number ( J:55400 )

• immature single-positive thymocytes from mutants injected with interferon-alpha are decreased 13-fold

endocrine/exocrine glands

abnormal thymus morphology ( J:55400 )

• 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

abnormal thymus cell ratio ( J:55400 , J:143472 )

• 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 Dll4^tm1Frad homozygous control mice (J:143472)

small thymus ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption have a small thymus

decreased thymocyte number ( J:55400 )

• mutants injected with interferon-alpha to induce partial gene disruption show a 5-fold reduction in thymocyte number