Phenotypes Associated with This Genotype

Genotype
MGI:3621814

• Allelic Composition: E2f1^tm1Meg/E2f1^tm1Meg
• Genetic Background: NOD.Cg-E2f1^tm1Meg

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

cellular

abnormal cell cycle ( J:93708 )

• fractions of cells in S phase from thymus and spleen of 5 week old mutant NOD mice are increased compared with wild-type, fractions of cells in G0-G1 in mutant thymus and spleen are reduced; in the spleen of mutants, number of cells in G2 and M phase are increased relative to wild-type

immune system

salivary gland inflammation ( J:93708 )

• large numbers of mononuclear inflammatory cells have infiltrated the salivary gland of 12-16 week old mutant NOD mice

enlarged thymus ( J:93708 )

• thymuses of 5 week old mutant NOD mice are enlarged with respect to wild-type NOD mice with a 55% increase in the number of thymocytes per thymus

insulitis ( J:93708 )

• large numbers of mononuclear inflammatory cells have infiltrated the salivary gland of 12-16 week old mutant NOD mice

abnormal double-positive T cell morphology ( J:93708 )

• null animals have lower numbers of double-positive Tcells than wild-type NOD animals

decreased double-positive T cell number ( J:93708 )

• null animals have lower numbers of double-positive Tcells than wild-type NOD animals

decreased regulatory T cell number ( J:93708 )

• numbers of CD4+CD25+ immunoregulatory T cells in the spleen of mutant NOD mice are decreased compared to wild-type NOD mice

increased T cell number ( J:93708 )

• mutant NOD mice have a greater absolute number of speen T cells

increased thymocyte number ( J:93708 )

• total numbers of thymocytes per thymus and absolute number of cells in all thymocyte populations are significantly increased in null NOD mice compared to wild-type NOD mice

abnormal CD4-positive, alpha beta T cell morphology ( J:93708 )

• thymuses of 5 week old null NOD mice contain more mature CD4+ cells than wild-type NOD animals

abnormal CD8-positive, alpha beta T cell morphology ( J:93708 )

• thymuses of 5 week old null NOD mice contain more mature CD8+ cells than wild-type NOD animals

increased interferon-gamma secretion ( J:93708 )

• spleen cells from null NOD mice stimulated with anti-CD3 produce increased levels of IFN gamma

increased interleukin-4 secretion ( J:93708 )

• production of IL-4 by spleen cells from null NOD mice is greater than wild-type NOD cells

increased susceptibility to autoimmune diabetes ( J:93708 )

• incidence of diabetes in knockout female mice is 88% and 58% in male mice, compared with 71% of female wild-type and 25% of male wild-type NOD mice by 32 weeks of age; time of onset is earlier and severity of diabetes is greater in knockouts than wild type littermates

• splenocytes from young mutant NOD mice can induce lympocytic infiltration of the salivary glands and pancreas and induce development of diabetes by spleen T cells from mutant NOD mice transferred into NOD.SCID recipients

endocrine/exocrine glands

decreased salivation ( J:93708 )

• knockout mice on the NOD background have reduced salivary flow rates than NOD or E2f1 knockout controls or the standard (NOD x B10.D2) F1 mice

salivary gland inflammation ( J:93708 )

• large numbers of mononuclear inflammatory cells have infiltrated the salivary gland of 12-16 week old mutant NOD mice

abnormal pancreatic islet morphology ( J:93708 )

• mononuclear inflammatory cells have infiltrated the pancreas islets of 12-16 week old prediabetic mutant NOD mice; there is some evidence of acinar cell degeneration and abnormally large nuclei or nuclei doubled in number are bserved

enlarged thymus ( J:93708 )

• thymuses of 5 week old mutant NOD mice are enlarged with respect to wild-type NOD mice with a 55% increase in the number of thymocytes per thymus

increased thymocyte number ( J:93708 )

• total numbers of thymocytes per thymus and absolute number of cells in all thymocyte populations are significantly increased in null NOD mice compared to wild-type NOD mice

insulitis ( J:93708 )

• large numbers of mononuclear inflammatory cells have infiltrated the salivary gland of 12-16 week old mutant NOD mice

hematopoietic system

enlarged thymus ( J:93708 )

• thymuses of 5 week old mutant NOD mice are enlarged with respect to wild-type NOD mice with a 55% increase in the number of thymocytes per thymus

abnormal double-positive T cell morphology ( J:93708 )

• null animals have lower numbers of double-positive Tcells than wild-type NOD animals

decreased double-positive T cell number ( J:93708 )

• null animals have lower numbers of double-positive Tcells than wild-type NOD animals

decreased regulatory T cell number ( J:93708 )

• numbers of CD4+CD25+ immunoregulatory T cells in the spleen of mutant NOD mice are decreased compared to wild-type NOD mice

increased T cell number ( J:93708 )

• mutant NOD mice have a greater absolute number of speen T cells

increased thymocyte number ( J:93708 )

• total numbers of thymocytes per thymus and absolute number of cells in all thymocyte populations are significantly increased in null NOD mice compared to wild-type NOD mice

abnormal CD4-positive, alpha beta T cell morphology ( J:93708 )

• thymuses of 5 week old null NOD mice contain more mature CD4+ cells than wild-type NOD animals

abnormal CD8-positive, alpha beta T cell morphology ( J:93708 )

• thymuses of 5 week old null NOD mice contain more mature CD8+ cells than wild-type NOD animals

digestive/alimentary system

decreased salivation ( J:93708 )

• knockout mice on the NOD background have reduced salivary flow rates than NOD or E2f1 knockout controls or the standard (NOD x B10.D2) F1 mice

salivary gland inflammation ( J:93708 )

• large numbers of mononuclear inflammatory cells have infiltrated the salivary gland of 12-16 week old mutant NOD mice

homeostasis/metabolism

decreased salivation ( J:93708 )

• knockout mice on the NOD background have reduced salivary flow rates than NOD or E2f1 knockout controls or the standard (NOD x B10.D2) F1 mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:93708
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:93708