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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Icostm1Flv
targeted mutation 1, Richard A Flavell
MGI:2683635
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
 		Icostm1Flv/Icostm1Flv involves: 129/Sv * C57BL/6 MGI:2683647
hm2
 		Icostm1Flv/Icostm1Flv involves: 129S1/Sv MGI:3851525
hm3
 		Icostm1Flv/Icostm1Flv NOD.129S1-Icostm1Flv MGI:3844531
ht4
 		Icostm1Flv/Icos+ NOD.129S1-Icostm1Flv MGI:3844532
cx5
 		Cd86tm2Shr/Cd86tm2Shr
Icostm1Flv/Icostm1Flv 		involves: 129S1/Sv * 129S4/SvJaeSor MGI:3851527
cx6
 		Icostm1Flv/Icostm1Flv
Tg(TcraTcrb)425Cbn/0 		involves: 129S1/Sv * C57BL/6 MGI:3851526
cx7
 		Icostm1Flv/Icostm1Flv
Tg(Cd4-Maf)6666Glm/0 		involves: 129S1/Sv * C57BL/6 MGI:3851534
cx8
 		Icostm1Flv/Icostm1Flv
Rc3h1san/Rc3h1+ 		involves: 129S1/Sv * C57BL/6 * C57BL/6JSfdAnu MGI:5445418


Genotype
MGI:2683647
hm1
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Genetic
Background		 involves: 129/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:87123 )
N
• T lymphocyte development normal in the thymus
decreased IgE level ( J:87123 )
• production of IgE reduced
decreased IgG1 level ( J:87123 )
• reduction of IgG1 levels
abnormal T-helper 2 physiology ( J:87123 )
• defect indicated by low Il-4 levels and low IgG1 and IgE levels
• Th2 differentiation normal but function disrupted
abnormal interferon level ( J:87123 )
• Ifn-gamma levels were normal to slightly increased
abnormal interleukin level ( J:87123 )
• Il-2 production defective
• Il-4 production very low
• Il-10 levels normal
• Il-13 levels reduced
small lymph nodes ( J:87123 )
• lymph nodes were small in immunized mice
• about 1/2 as many cells/node as in wild-type mice
increased susceptibility to experimental autoimmune encephalomyelitis ( J:87123 )
• greater succeptibility to experimental autoimmune encephalitis

homeostasis/metabolism
abnormal interferon level ( J:87123 )
• Ifn-gamma levels were normal to slightly increased
abnormal interleukin level ( J:87123 )
• Il-2 production defective
• Il-4 production very low
• Il-10 levels normal
• Il-13 levels reduced

hematopoietic system
decreased IgE level ( J:87123 )
• production of IgE reduced
decreased IgG1 level ( J:87123 )
• reduction of IgG1 levels
abnormal T-helper 2 physiology ( J:87123 )
• defect indicated by low Il-4 levels and low IgG1 and IgE levels
• Th2 differentiation normal but function disrupted

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
common variable immunodeficiency DOID:12177 OMIM:PS607594
 J:87123




Genotype
MGI:3851525
hm2
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Genetic
Background		 involves: 129S1/Sv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal cytokine secretion ( J:112600 )
• T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce less IL-4, IL-17a and interferon gamma than wild-type in response to KLH restimulation




Genotype
MGI:3844531
hm3
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Genetic
Background		 NOD.129S1-Icostm1Flv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
immune system phenotype ( J:131529 )
N
• development of lymphocytes is normal
insulitis ( J:131529 )
• only a few mice develop marginal levels of inflammation of the islets
decreased T cell number ( J:131529 )
• the number of CD25+ and FoxP3+ CD4 T cells in the periphery and pancreatic draining lymph nodes is decreased 30% compared to in heterozygotes
• the frequency of IFN-gamma+ T cells is decreased compared to in heterozygous mice
decreased interferon-gamma secretion ( J:131529 )
• the frequency of IFN-gamma+ T cells is decreased compared to in heterozygous mice
decreased susceptibility to autoimmune diabetes ( J:131529 )
• after 60 weeks, no mice develop diabetes compared with 65% of heterozygotes and 75% in wild-type NOD mice
decreased autoantibody level ( J:131529 )
• anti-GAD65 and anti-insulin antibodies are decreased 3- to 5-fold compared to in heterozygotes
decreased anti-insulin autoantibody level ( J:131529 )
• decreased 3- to 5-fold compared to in heterozygotes

endocrine/exocrine glands
endocrine/exocrine gland phenotype ( J:131529 )
N
• mice exhibit normal numbers of pancreatic islets
insulitis ( J:131529 )
• only a few mice develop marginal levels of inflammation of the islets

hematopoietic system
decreased T cell number ( J:131529 )
• the number of CD25+ and FoxP3+ CD4 T cells in the periphery and pancreatic draining lymph nodes is decreased 30% compared to in heterozygotes
• the frequency of IFN-gamma+ T cells is decreased compared to in heterozygous mice




Genotype
MGI:3844532
ht4
Allelic
Composition		 Icostm1Flv/Icos+
Genetic
Background		 NOD.129S1-Icostm1Flv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
insulitis ( J:131529 )
• severe

immune system
insulitis ( J:131529 )
• severe




Genotype
MGI:3851527
cx5
Allelic
Composition		 Cd86tm2Shr/Cd86tm2Shr
Icostm1Flv/Icostm1Flv
Genetic
Background		 involves: 129S1/Sv * 129S4/SvJaeSor
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd86tm2Shr mutation (3 available); any Cd86 mutation (38 available)
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal cytokine level ( J:112600 )
• T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce no IL-4, IL-17a or interferon gamma in response to KLH restimulation

homeostasis/metabolism
abnormal cytokine level ( J:112600 )
• T cells from mice immunized with keyhole limpet hemocyanin (KLH) in CFA (conjugated Freund's adjuvant) produce no IL-4, IL-17a or interferon gamma in response to KLH restimulation




Genotype
MGI:3851526
cx6
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Tg(TcraTcrb)425Cbn/0
Genetic
Background		 involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
Tg(TcraTcrb)425Cbn mutation (3 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal cytokine secretion ( J:112600 )
• naive CD4 T cells cultured with OVA peptide-loaded wild-type splenic antigen presenting cells (APCs) and restimulated with anti-CD3 and secrete less IL-4 and IL-17a and more interferon gamma (Ifng) than stimulated wild-type CD4 T cells
• CD4 T cells cultured with OVA peptide-loaded spleen cells from B7 (CD80/86) deficient mice then restimulated with anti-CD3 do not produce IL-4, IL-17a or Ifng




Genotype
MGI:3851534
cx7
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Tg(Cd4-Maf)6666Glm/0
Genetic
Background		 involves: 129S1/Sv * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
Tg(Cd4-Maf)6666Glm mutation (0 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal cytokine secretion ( J:112600 )
• T cells activated for 4 days with anti-CD3 and wild-type antigen presenting cells produce more IL-4 than controls but production of IL-17a and interferon gamma is much lower




Genotype
MGI:5445418
cx8
Allelic
Composition		 Icostm1Flv/Icostm1Flv
Rc3h1san/Rc3h1+
Genetic
Background		 involves: 129S1/Sv * C57BL/6 * C57BL/6JSfdAnu
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Icostm1Flv mutation (3 available); any Icos mutation (35 available)
Rc3h1san mutation (7 available); any Rc3h1 mutation (42 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased T cell derived lymphoma incidence ( J:189087 )
• 5 of 25 double mutants develop T cell lymphoma
decreased lymphoma incidence ( J:189087 )
• tumor incidence (about 20%) is reduced compared to Rc3h1 heterozygotes (more than 50%)

endocrine/exocrine glands
increased T cell derived lymphoma incidence ( J:189087 )
• 5 of 25 double mutants develop T cell lymphoma




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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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04/30/2024
MGI 6.23 		The Jackson Laboratory