Phenotypes Associated with This Genotype

Genotype
MGI:6278552

• Allelic Composition: C9orf72^tm1Eggn/C9orf72^tm1Eggn
• 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 an increased risk of death as mice age

growth/size/body

cachexia ( J:240357 )

• mice show decreased weight with age

• mice begin declining on average at 76 +/- 51 days

enlarged liver ( J:240357 )

• a small percentage of mice develop hepatomegaly

enlarged spleen ( J:240357 )

• spleen is enlarged in end-stage mice

hematopoietic system

enlarged spleen ( J:240357 )

• spleen is enlarged in end-stage mice

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 )

increased leukocyte cell number ( J:240357 )

• total white blood cell counts are modestly but significantly elevated

increased neutrophil cell number ( J:240357 )

• increase in the number of circulating neutrophils

abnormal lymphocyte morphology ( J:240357 )

• lymphocytic stromal cell hyperplasia

homeostasis/metabolism

abnormal circulating cytokine level ( J:240357 )

• 18 of 36 cytokines and chemokines are elevated in the plasma, 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

enlarged spleen ( J:240357 )

• spleen is enlarged in end-stage mice

increased leukocyte cell number ( J:240357 )

• total white blood cell counts are modestly but significantly elevated

increased neutrophil cell number ( J:240357 )

• increase in the number of circulating neutrophils

abnormal lymphocyte morphology ( J:240357 )

• lymphocytic stromal cell hyperplasia

abnormal circulating cytokine level ( J:240357 )

• 18 of 36 cytokines and chemokines are elevated in the plasma, 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

enlarged cervical lymph nodes ( J:240357 )

• a subset of end-stage mice develop enlarged cervical lymph nodes

• both B and T cells are greatly expanded within the lymph nodes

increased susceptibility to autoimmune disorder ( J:240357 )

• mice develop classic features of autoimmunity including anti-dsDNA antibodies and increased cytokine and chemokine levels

• wild-type recipients transplanted with homozygous mutant bone marrow are smaller, have larger spleens, some have enlarged cervical lymph nodes, lower platelet count, reduced hematocrit, elevated cytokines, and elevated anti-dsDNA antibody activity indicating autoimmunity development

• homozygous mutant recipients transplanted with wild-type bone marrow show increased weight, increased life span, decreased level of splenomegaly, fewer neutrophils, elevated platelet counts, reduced cytokine levels and reduced anti-dsDNA activity

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

• mice exhibit an accumulation of anti-dsDNA antibody which is sustained in plasma in mice greater than 300 days of age

dermatitis ( J:240357 )

integument

dermatitis ( J:240357 )

liver/biliary system

enlarged liver ( J:240357 )

• a small percentage of mice develop hepatomegaly

cardiovascular system

internal hemorrhage ( J:240357 )

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