Phenotypes associated with this allele

• Allele Symbol: Csnk1a1^{tm1c(KOMP)Wtsi}
• Allele Name: targeted mutation 1c, Wellcome Trust Sanger Institute
• Allele ID: MGI:5762595
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Csnk1a1^tm1c(KOMP)Wtsi/Csnk1a1^tm1c(KOMP)Wtsi Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * C57BL/6N * CBA	MGI:5762596
cn2	Csnk1a1^tm1c(KOMP)Wtsi/Csnk1a1^+ Tg(Mx1-cre)1Cgn/0	involves: C57BL/6 * C57BL/6N * CBA	MGI:5762598

Genotype
MGI:5762596

cn1

• Allelic Composition: Csnk1a1^{tm1c(KOMP)Wtsi}/Csnk1a1^{tm1c(KOMP)Wtsi}; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA
• Cell Lines: EPD0270_3_B02

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

mortality/aging

premature death ( J:216977 )

• mice die 5-17 days after induction with polyinosinic-polycytidylic acid [poly(I:C)]

cardiovascular system

abnormal myocardium layer morphology ( J:216977 )

• areas of the myocardium show wavy fibers with loss of transversal striations, partially with loss of the cell nucleus following poly(I:C) induction

cardiac ischemia ( J:216977 )

• myocardium shows signs of ischemia following poly(I:C) induction

hematopoietic system

abnormal blood cell morphology ( J:216977 )

• mice exhibit a decrease in all peripheral blood counts after induction with poly(I:C)

extramedullary hematopoiesis ( J:216977 )

• seen following poly(I:C) induction

decreased hematopoietic stem cell number ( J:216977 )

• 10 days after poly(I:C) treatment, mice show a reduction in hematopoietic stem cells (LSK; Lin^lowSca-1+ckit+), including long-term (LT; Lin^lowSca-1+ckit+CD150+CD48-) and short-term (ST; Lin^lowSca-1+ckit+CD150-CD48-) hematopoietic stem cells and multipotent progenitor cells (MPPs; Lin^lowSca-1+ckit+CD150-CD48+)

abnormal spleen red pulp morphology ( J:216977 )

• rarefication of the red pulp is seen following poly(I:C) induction

abnormal hematopoietic stem cell physiology ( J:216977 )

• a greater number of LSK cells are undergoing early and late apoptosis after induction with poly(I:C) compared to controls

• hematopoietic stem cells (HSC) from mice induced with poly(I:C) exit quiescence and enter the cell cycle, with a decrease in the number of HSC (LSK) in G0 and an increase in S/G2/M compared to control cells

bone marrow failure ( J:216977 )

• mice show evidence of fulminant bone marrow failure with evidence of ischemia in multiple organs after induction with poly(I:C)

• lethally irradiated wild-type mice transplanted with mutant whole bone marrow cells become moribund with bone marrow failure 8-14 days after poly(I:C) treatment, with a complete loss of HSPCs

immune system

abnormal spleen red pulp morphology ( J:216977 )

• rarefication of the red pulp is seen following poly(I:C) induction

bone marrow failure ( J:216977 )

• mice show evidence of fulminant bone marrow failure with evidence of ischemia in multiple organs after induction with poly(I:C)

• lethally irradiated wild-type mice transplanted with mutant whole bone marrow cells become moribund with bone marrow failure 8-14 days after poly(I:C) treatment, with a complete loss of HSPCs

liver/biliary system

abnormal liver morphology ( J:216977 )

• cytoplasmic vacuolization and pyknotic nuclei are seen in the liver following poly(I:C) induction

abnormal liver physiology ( J:216977 )

• liver shows signs of ischemia following poly(I:C) induction

muscle

abnormal myocardium layer morphology ( J:216977 )

• areas of the myocardium show wavy fibers with loss of transversal striations, partially with loss of the cell nucleus following poly(I:C) induction

Genotype
MGI:5762598

cn2

• Allelic Composition: Csnk1a1^{tm1c(KOMP)Wtsi}/Csnk1a1⁺; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6N * CBA
• Cell Lines: EPD0270_3_B02

mortality/aging

premature death ( J:216977 )

• survival of polyinosinic-polycytidylic acid [poly(I:C)] treated mice is impaired

hematopoietic system

abnormal hematopoietic system morphology/development ( J:216977 )

• lethally irradiated wild-type mice transplanted with mutant whole bone marrow cells show full reconstitution of the bone marrow, normal hemoglobin, elevated white blood cell counts with lymphocytosis, and bone marrow with mildly dysplastic hypolobulated micro-megakaryoctyes in atypical locations 8 weeks after poly(I:C) induction and mice develop elevated platelet count over time

decreased common myeloid progenitor cell number ( J:216977 )

• 15 months after poly(I:C) treatment, mice show a near-complete loss of myeloid progenitor cells

decreased bone marrow cell number ( J:216977 )

• 8 weeks after poly(I:C) treatment, a reduction in bone marrow cellularity and in the percentage of long-term (LT; Lin^lowSca-1+ckit+CD150+CD48-) and short-term (ST; Lin^lowSca-1+ckit+CD150-CD48-) hematopoietic stem cells is seen

abnormal megakaryocyte morphology ( J:216977 )

• hypolobulated micro-megakaryocytes are seen 8 weeks after poly(I:C) induction

• whole bone marrow cells cultured in vitro in the presence of thrombopoietin show that CD41+ megakaryocytes shift toward hypoploidy

decreased myeloid cell number ( J:216977 )

• reduction of the myeloid lineage 15 months after poly(I:C) induction

decreased hematopoietic stem cell number ( J:216977 )

• 8 weeks after poly(I:C) treatment, a reduction in the percentage of long-term (LT; Lin^lowSca-1+ckit+CD150+CD48-) and short-term (ST; Lin^lowSca-1+ckit+CD150-CD48-) hematopoietic stem cells is seen 15 months after poly(I:C) treatment, mice show a decrease in the LT-HSCs and ST-HSCs

pancytopenia ( J:216977 )

• 15 months after poly(I:C) treatment, mice develop pancytopenia

abnormal erythroid lineage cell morphology ( J:216977 )

• reduction of the erythroid lineage 15 months after poly(I:C) induction