Phenotypes Associated with This Genotype

Genotype
MGI:6278554

• Allelic Composition: C9orf72^tm1.1Eggn/C9orf72^tm1.1Eggn
• Genetic Background: involves: C57BL/6 * C57BL/6N

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

mortality/aging

premature death ( J:240357 )

• mice exhibit increased mortality at later ages

growth/size/body

cachexia ( J:240357 )

• mice show decreased weight with age

• mice begin declining on average at 37 +/- 29 days

enlarged liver ( J:240357 )

• a small percentage of mice develop hepatomegaly

enlarged spleen ( J:240357 )

• spleens are enlarged at P50 but not at P25

hematopoietic system

microcytic anemia ( J:240357 )

• modest microcytic anemia

decreased erythrocyte cell number ( J:240357 )

• modest but significant reduction in red blood cells

decreased hematocrit ( J:240357 )

• modest but significant reduction in hematocrit

decreased mean corpuscular volume ( J:240357 )

thrombocytopenia ( J:240357 )

• platelet count is already reduced by P50 and is persistently depressed in older mice

increased leukocyte cell number ( J:240357 )

• total white blood cell counts are modestly but significantly elevated

increased neutrophil cell number ( J:240357 )

• mice begin to exhibit a persistent and significant increase in neutrophil numbers at 100 days of age

abnormal lymphocyte morphology ( J:240357 )

• lymphocytic stromal cell hyperplasia

increased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:240357 )

• CD25+CD4+ T cells are elevated in spleens of P400 mice

abnormal spleen morphology ( J:240357 )

• spleens display a disruption of red and white pulp boundaries

• analysis of V(D)J recombination in spleens shows polyclonal populations of B and T cells

enlarged spleen ( J:240357 )

• spleens are enlarged at P50 but not at P25

increased splenocyte number ( J:240357 )

• mice show an increase in splenocytes derived from several lineages, including CD19+B220+ cells, CD3+CD4+ T cells, and CD11b+Ly6G+ neutrophils

• however, no histological changes in cellularity of the bone marrow is seen

increased IgG level ( J:240357 )

• IgG autoantibodies targeting 113 of 124 antigens are elevated

increased IgM level ( J:240357 )

• IgM autoantibodies targeting 117 of 124 antigens are elevated

homeostasis/metabolism

abnormal circulating cytokine level ( J:240357 )

• at 50 days of age, IL-31, IL15/IL-15R, and GM-CSF are elevated in plasma

• 18 of 36 cytokines and chemokines are elevated in the plasma at P100-300, including IL-22, IL-28, IL-23, IL-6, MCP-1, IL-31, IL-5, IL-10, IL-1beta, IL-15/IL-15R, IFN-gamma, IL-3, GM-CSF, IL-17A, IFN-alpha, MIP-1B, LIF, and growth-related oncogene alpha

immune system

increased leukocyte cell number ( J:240357 )

• total white blood cell counts are modestly but significantly elevated

increased neutrophil cell number ( J:240357 )

• mice begin to exhibit a persistent and significant increase in neutrophil numbers at 100 days of age

abnormal lymphocyte morphology ( J:240357 )

• lymphocytic stromal cell hyperplasia

increased CD4-positive, CD25-positive, alpha-beta regulatory T cell number ( J:240357 )

• CD25+CD4+ T cells are elevated in spleens of P400 mice

abnormal spleen morphology ( J:240357 )

• spleens display a disruption of red and white pulp boundaries

• analysis of V(D)J recombination in spleens shows polyclonal populations of B and T cells

enlarged spleen ( J:240357 )

• spleens are enlarged at P50 but not at P25

increased splenocyte number ( J:240357 )

• mice show an increase in splenocytes derived from several lineages, including CD19+B220+ cells, CD3+CD4+ T cells, and CD11b+Ly6G+ neutrophils

• however, no histological changes in cellularity of the bone marrow is seen

increased IgG level ( J:240357 )

• IgG autoantibodies targeting 113 of 124 antigens are elevated

increased IgM level ( J:240357 )

• IgM autoantibodies targeting 117 of 124 antigens are elevated

abnormal circulating cytokine level ( J:240357 )

• at 50 days of age, IL-31, IL15/IL-15R, and GM-CSF are elevated in plasma

• 18 of 36 cytokines and chemokines are elevated in the plasma at P100-300, including IL-22, IL-28, IL-23, IL-6, MCP-1, IL-31, IL-5, IL-10, IL-1beta, IL-15/IL-15R, IFN-gamma, IL-3, GM-CSF, IL-17A, IFN-alpha, MIP-1B, LIF, and growth-related oncogene alpha

increased susceptibility to autoimmune disorder ( J:240357 )

• mice develop classic features of autoimmunity

increased autoantibody level ( J:240357 )

• IgM autoantibodies targeting 117 of 124 antigens and IgG autoantibodies targeting 113 of 124 antigens are elevated

increased anti-double stranded DNA antibody level ( J:240357 )

• mice exhibit accumulation of anti-dsDNA antibody between P50 and P100

brain inflammation ( J:240357 )

• mice show increased neural inflammation in the cortex

liver inflammation ( J:240357 )

• immune cell infiltrates in the liver

dermatitis ( J:240357 )

integument

dermatitis ( J:240357 )

liver/biliary system

enlarged liver ( J:240357 )

• a small percentage of mice develop hepatomegaly

liver inflammation ( J:240357 )

• immune cell infiltrates in the liver

nervous system

nervous system phenotype ( J:240357 )

N • number of spinal motor neurons is normal and no gross abnormalities of the motor cortex or other regions of the brain are seen

brain inflammation ( J:240357 )

• mice show increased neural inflammation in the cortex

respiratory system

respiratory failure ( J:240357 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autoimmune disease		DOID:417	OMIM:109100	J:240357