Phenotypes associated with this allele

• Allele Symbol: Itk^tm1Litt
• Allele Name: targeted mutation 1, Dan R Littman
• Allele ID: MGI:2178820
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Itk^tm1Litt/Itk^tm1Litt	B6.129S4-Itk^tm1Litt	MGI:3841990
hm2	Itk^tm1Litt/Itk^tm1Litt	involves: 129S4/SvJae	MGI:3771573
hm3	Itk^tm1Litt/Itk^tm1Litt	involves: 129S4/SvJae * C57BL/6	MGI:3771839
hm4	Itk^tm1Litt/Itk^tm1Litt	involves: 129S4/SvJae * C57BL/6J	MGI:2652156
cx5	Cblb^tm1Pngr/Cblb^tm1Pngr Itk^tm1Litt/Itk^tm1Litt	B6.129-Itk^tm1Litt Cblb^tm1Pngr	MGI:3841993
cx6	Itk^tm1Litt/Itk^tm1Litt Vav1^tm2Bbd/Vav1^tm2Bbd	B6.129-Itk^tm1Litt Vav1^tm2Bbd	MGI:3841989
cx7	Itk^tm1Litt/Itk^tm1Litt Txk^tm1Pls/Txk^tm1Pls	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:2652142
cx8	Itk^tm1Litt/Itk^tm1Litt Tg(DO11.10)10Dlo/0	involves: 129S4/SvJae * BALB/c * C3H * C57BL/6J	MGI:3771808
cx9	Il4^tm1Lky/Il4^tm1Lky Itk^tm1Litt/Itk^tm1Litt	involves: 129S4/SvJae * BALB/c * C57BL/6J	MGI:3771807
cx10	Il15^tm1Imx/Il15^tm1Imx Itk^tm1Litt/Itk^tm1Litt	involves: 129S4/SvJae * C57BL/6	MGI:3771841
cx11	Itk^tm1Litt/Itk^tm1Litt Tg(TcraH-Y,TcrbH-Y)71Vbo/0	involves: 129S4/SvJae * C57BL/6 * DBA/2J	MGI:3771702
cx12	Itk^tm1Litt/Itk^tm1Litt Tg(TcrAND)53Hed/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:3771701

Genotype
MGI:3841990

hm1

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: B6.129S4-Itk^tm1Litt

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

immune system

decreased T cell proliferation ( J:141390 )

• in response to loading with CFSE followed by stimulation with anti-CD3

abnormal T cell morphology ( J:141390 )

• most remaining single positive T cells have an activated/memory like phenotype

abnormal positive T cell selection ( J:141390 )

• TCR dependent Ca2+ mobilization is reduced

increased double-negative T cell number ( J:141390 )

decreased T cell number ( J:141390 )

• decrease in the number of peripheral T cells

decreased interleukin-2 secretion ( J:141390 )

• in response to anti-CD3 anti-CD28 costimulation

hematopoietic system

decreased T cell proliferation ( J:141390 )

• in response to loading with CFSE followed by stimulation with anti-CD3

abnormal T cell morphology ( J:141390 )

• most remaining single positive T cells have an activated/memory like phenotype

abnormal positive T cell selection ( J:141390 )

• TCR dependent Ca2+ mobilization is reduced

increased double-negative T cell number ( J:141390 )

decreased T cell number ( J:141390 )

• decrease in the number of peripheral T cells

cellular

decreased T cell proliferation ( J:141390 )

• in response to loading with CFSE followed by stimulation with anti-CD3

Genotype
MGI:3771573

hm2

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: involves: 129S4/SvJae

immune system

decreased T cell proliferation ( J:54449 )

• mice show variable defects in CD4+ T cell proliferation

increased susceptibility to parasitic infection ( J:54449 )

• mice infected with Toxoplasma gondii survive the early infection which requires natural killer cells; mean survival time of 69 days

hematopoietic system

decreased T cell proliferation ( J:54449 )

• mice show variable defects in CD4+ T cell proliferation

cellular

decreased T cell proliferation ( J:54449 )

• mice show variable defects in CD4+ T cell proliferation

Genotype
MGI:3771839

hm3

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: involves: 129S4/SvJae * C57BL/6

immune system

abnormal thymus cell ratio ( J:111786 )

• number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age

• slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi

• CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type

• absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type

• at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells

abnormal CD8-positive, alpha-beta T cell differentiation ( J:111786 )

• defects in thymic development of CD44^loCD122^loCD8+ T cells are detected

decreased CD8-positive, alpha-beta T cell number ( J:111786 )

• in blood, mice lack CD8+CD44^loCD122^lo T cells and total CD8+ T cell number is reduced to 20-30% compared to wild-type

hematopoietic system

abnormal thymus cell ratio ( J:111786 )

• number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age

• slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi

• CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type

• absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type

• at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells

abnormal CD8-positive, alpha-beta T cell differentiation ( J:111786 )

• defects in thymic development of CD44^loCD122^loCD8+ T cells are detected

decreased CD8-positive, alpha-beta T cell number ( J:111786 )

• in blood, mice lack CD8+CD44^loCD122^lo T cells and total CD8+ T cell number is reduced to 20-30% compared to wild-type

endocrine/exocrine glands

abnormal thymus cell ratio ( J:111786 )

• number of CD8 single-positive thymocytes is increased relative to wild-type at 3 weeks of age

• slight increase in number of CD24^hi CD8 SP thymocytes is seen relative to wild-type thymi; absolute number of CD24^int CD8 SP thymocytes is decreased to <50% of wild-type thymi

• CD24^lo CD8 SP thymocytes which are considered mature show an increase in number relative to wild-type

• absolute number of CD122^hi cells are increased in number at all stages of T cell development compared to wild-type

• at mature CD40^lo stage, thymi contain essentially no CD122^lo CD8 SP T cells

Genotype
MGI:2652156

hm4

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

immune system

immune system phenotype ( J:31230 )

N • cell numbers in lymph nodes and spleen are unchanged relative to controls

decreased T cell proliferation ( J:31230 )

• in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates

• CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls

• CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised

decreased B cell number ( J:31230 )

• number of B cells is increased in concert with reduction of T cell numbers

decreased T cell number ( J:31230 )

• number of T cells is reduced by 1.5- to 2-fold compared to controls

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• ratio of CD4 single positive thymocytes versus CD8 SP thymocytes is reduced 2-3-fold compared to heterozygous or wild-type littermates

• number and proportion of CD4+ T cells in periphery show a more marked reduction than CD8+ T cells

hematopoietic system

decreased T cell proliferation ( J:31230 )

• in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates

• CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls

• CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised

decreased B cell number ( J:31230 )

• number of B cells is increased in concert with reduction of T cell numbers

decreased T cell number ( J:31230 )

• number of T cells is reduced by 1.5- to 2-fold compared to controls

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• ratio of CD4 single positive thymocytes versus CD8 SP thymocytes is reduced 2-3-fold compared to heterozygous or wild-type littermates

• number and proportion of CD4+ T cells in periphery show a more marked reduction than CD8+ T cells

cellular

decreased T cell proliferation ( J:31230 )

• in response to allogeneic stimulation, lymph node CD4+ T cells show significantly reduced proliferation in a mixed lymphocyte reaction compared to control littermates

• CD4+ and CD8+ cells challenged with irradiated splenocytes from MHC class I or class II mutant mouse strains display significantly reduced proliferation compared to controls

• CD4+ T cells stimulated with concanavalin A or anti-CD3 antibodies in presence of syngeneic splenocytes show reduced proliferative responses indicating early phase of TCR-mediated signaling is compromised

Genotype
MGI:3841993

cx5

• Allelic Composition: Cblb^tm1Pngr/Cblb^tm1Pngr; Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: B6.129-Itk^tm1Litt Cblb^tm1Pngr

immune system

immune system phenotype ( J:141390 )

N • T cell proliferation in response to loading with CFSE followed by stimulation with anti-CD3 is similar to controls, unlike in either single null mouse

abnormal T cell morphology ( J:141390 )

• similar to mice homozygous null for Itk alone, most T cells have an activated/memory like phenotype

abnormal T-helper 2 cell differentiation ( J:141390 )

• partial rescue of defect in Th2 polarization compared to mice homozygous null for Itk alone

decreased T cell number ( J:141390 )

• decrease in T cell numbers similar to that in mice homozygous null for Itk alone

decreased interleukin-2 secretion ( J:141390 )

• partial rescue of decreased IL2 secretion in response to anti-CD3 anti-CD28 costimulation compared to mice homozygous null for Itk alone

hematopoietic system

abnormal T cell morphology ( J:141390 )

• similar to mice homozygous null for Itk alone, most T cells have an activated/memory like phenotype

abnormal T-helper 2 cell differentiation ( J:141390 )

• partial rescue of defect in Th2 polarization compared to mice homozygous null for Itk alone

decreased T cell number ( J:141390 )

• decrease in T cell numbers similar to that in mice homozygous null for Itk alone

Genotype
MGI:3841989

cx6

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt; Vav1^tm2Bbd/Vav1^tm2Bbd
• Genetic Background: B6.129-Itk^tm1Litt Vav1^tm2Bbd

immune system

increased B cell number ( J:141390 )

• slight but significant increase in the number of B cells compared to wild-type mice

abnormal T cell morphology ( J:141390 )

• most remaining single positive T cells have an activated/memory like phenotype

abnormal CD4-positive T cell differentiation ( J:141390 )

• virtually no CD4+ cells have a mature phenotype

abnormal CD8-positive, alpha-beta T cell differentiation ( J:141390 )

• lack of cells with a CD3^hi phenotype

abnormal positive T cell selection ( J:141390 )

• the CD69+ subset is almost completely absent and TCR dependent Ca2+ mobilization is nearly abolished

decreased T cell number ( J:141390 )

• dramatic loss of peripheral T cells

• lymph node T cell numbers are about 4 fold lower compared to mice homozygous null for Vav1 alone

decreased thymocyte number ( J:141390 )

• compared to mice homozygous null for Vav1 alone

decreased double-positive T cell number ( J:141390 )

• compared to wild-type mice and mice homozygous for either allele alone

• relative increase in the DN3 subset is similar to mice homozygous null for Vav1 alone

decreased CD4-positive, alpha-beta T cell number ( J:141390 )

decreased CD8-positive, alpha-beta T cell number ( J:141390 )

abnormal T cell physiology ( J:141390 )

• dramatic reduction in double positive T cell half-life compared to wild-type cells

increased T cell apoptosis ( J:141390 )

• compared to wild-type mice or mice homozygous for either allele alone

• increase in early apoptotic cells in the double positive cell population

hematopoietic system

increased B cell number ( J:141390 )

• slight but significant increase in the number of B cells compared to wild-type mice

abnormal T cell morphology ( J:141390 )

• most remaining single positive T cells have an activated/memory like phenotype

abnormal CD4-positive T cell differentiation ( J:141390 )

• virtually no CD4+ cells have a mature phenotype

abnormal CD8-positive, alpha-beta T cell differentiation ( J:141390 )

• lack of cells with a CD3^hi phenotype

abnormal positive T cell selection ( J:141390 )

• the CD69+ subset is almost completely absent and TCR dependent Ca2+ mobilization is nearly abolished

decreased T cell number ( J:141390 )

• dramatic loss of peripheral T cells

• lymph node T cell numbers are about 4 fold lower compared to mice homozygous null for Vav1 alone

decreased thymocyte number ( J:141390 )

• compared to mice homozygous null for Vav1 alone

decreased double-positive T cell number ( J:141390 )

• compared to wild-type mice and mice homozygous for either allele alone

• relative increase in the DN3 subset is similar to mice homozygous null for Vav1 alone

decreased CD4-positive, alpha-beta T cell number ( J:141390 )

decreased CD8-positive, alpha-beta T cell number ( J:141390 )

abnormal T cell physiology ( J:141390 )

• dramatic reduction in double positive T cell half-life compared to wild-type cells

increased T cell apoptosis ( J:141390 )

• compared to wild-type mice or mice homozygous for either allele alone

• increase in early apoptotic cells in the double positive cell population

cellular

increased T cell apoptosis ( J:141390 )

• compared to wild-type mice or mice homozygous for either allele alone

• increase in early apoptotic cells in the double positive cell population

endocrine/exocrine glands

decreased thymocyte number ( J:141390 )

• compared to mice homozygous null for Vav1 alone

Genotype
MGI:2652142

cx7

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt; Txk^tm1Pls/Txk^tm1Pls
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

immune system

decreased T cell proliferation ( J:54449 )

• mature T cells fail to proliferate upon T cell receptor activation (by anti-CD3e or concanavalin A); proliferation defects are observed in both CD4+ and CD8+ populations

• proliferation defects are only partially overcome by exogenous Il-2

decreased CD4-positive, alpha-beta T cell number ( J:54449 )

• animals have reduced numbers of mature T cells, particularly CD4+ T cells, resulting in a decreased CD4:CD8 ratio

decreased single-positive T cell number ( J:54449 )

• numbers of CD4+ and CD8+ T cells are increased relative to Itk-null mice; however total T cell numbers are normal

increased susceptibility to parasitic infection ( J:54449 )

• mice infected with Toxoplasma gondii survive the early infection which requires natural killer cells, but by 30 days post-infection, mice are visibly ill and have a mean survival time of 41 days

• after 30 days, mice have increased numbers of brain cysts indicating defect in ability to limit infection

hematopoietic system

decreased T cell proliferation ( J:54449 )

• mature T cells fail to proliferate upon T cell receptor activation (by anti-CD3e or concanavalin A); proliferation defects are observed in both CD4+ and CD8+ populations

• proliferation defects are only partially overcome by exogenous Il-2

decreased CD4-positive, alpha-beta T cell number ( J:54449 )

• animals have reduced numbers of mature T cells, particularly CD4+ T cells, resulting in a decreased CD4:CD8 ratio

decreased single-positive T cell number ( J:54449 )

• numbers of CD4+ and CD8+ T cells are increased relative to Itk-null mice; however total T cell numbers are normal

cellular

decreased T cell proliferation ( J:54449 )

• mature T cells fail to proliferate upon T cell receptor activation (by anti-CD3e or concanavalin A); proliferation defects are observed in both CD4+ and CD8+ populations

• proliferation defects are only partially overcome by exogenous Il-2

Genotype
MGI:3771808

cx8

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt; Tg(DO11.10)10Dlo/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C3H * C57BL/6J

immune system

abnormal T-helper 2 physiology ( J:129883 )

• isolated T cells primed under Th2 conditions for 5 days, restimulated for 5 more days, then restimulated in absence of exogenous cytokine fail to produce Il4, although cell expansion is similar to wild-type; PMA/ionomycin restimulation of Th2-primed cells restores Il4 secretion

hematopoietic system

abnormal T-helper 2 physiology ( J:129883 )

• isolated T cells primed under Th2 conditions for 5 days, restimulated for 5 more days, then restimulated in absence of exogenous cytokine fail to produce Il4, although cell expansion is similar to wild-type; PMA/ionomycin restimulation of Th2-primed cells restores Il4 secretion

Genotype
MGI:3771807

cx9

• Allelic Composition: Il4^tm1Lky/Il4^tm1Lky; Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6J

immune system

immune system phenotype ( J:129883 )

N • both Th1 and Th2 programs can be induced in Itk-null cells when Th1 priming or Th2 priming conditions are used

abnormal T-helper 2 physiology ( J:129883 )

• upon restimulation with anti-TCR antibodies, numbers of Il4 (EGFP) expressing cells remains constant (~65%, elevated relative to wild-type cells) but Il4 protein production is markedly attenuated; however if TCR-mediated signaling is bypassed with stimulation by PMA/ionomycin, Th2-primed null cells show similar levels of Il4 secretion to wild-type cells

• similar results are obtained in vivo

abnormal cytokine secretion ( J:129883 )

• only Th1-primed cells can secrete effector cytokines (interferon gamma) upon restimulation; Th2-primed cells do not secrete Il4 upon restimulation as shown by Il4 reporter expression

• similar results are obtained in vivo

• after infection with Leishmania major, restimulation with L. major antigens reveals defects in Il4 production

abnormal response to infection ( J:129883 )

• after infection with Leishmania major, restimulation with L. major antigens reveals defects in Il4 production

cellular

abnormal cell death ( J:129883 )

• fewer Itk-null lymphocytes undergo activation induced cell death than wild-type cells upon restimulation

hematopoietic system

abnormal T-helper 2 physiology ( J:129883 )

• upon restimulation with anti-TCR antibodies, numbers of Il4 (EGFP) expressing cells remains constant (~65%, elevated relative to wild-type cells) but Il4 protein production is markedly attenuated; however if TCR-mediated signaling is bypassed with stimulation by PMA/ionomycin, Th2-primed null cells show similar levels of Il4 secretion to wild-type cells

• similar results are obtained in vivo

Genotype
MGI:3771841

cx10

• Allelic Composition: Il15^tm1Imx/Il15^tm1Imx; Itk^tm1Litt/Itk^tm1Litt
• Genetic Background: involves: 129S4/SvJae * C57BL/6

immune system

abnormal thymus cell ratio ( J:111786 )

• number of CD24^int CD8 SP thymocytes is less than that seen in Il15-null thymi at 3 weeks of age

• absolute number of CD122^hi cells is reduced in number among CD8+ T cells at all stages of T cell development compared to Itk-single null thymi

hematopoietic system

abnormal thymus cell ratio ( J:111786 )

• number of CD24^int CD8 SP thymocytes is less than that seen in Il15-null thymi at 3 weeks of age

• absolute number of CD122^hi cells is reduced in number among CD8+ T cells at all stages of T cell development compared to Itk-single null thymi

endocrine/exocrine glands

abnormal thymus cell ratio ( J:111786 )

• number of CD24^int CD8 SP thymocytes is less than that seen in Il15-null thymi at 3 weeks of age

• absolute number of CD122^hi cells is reduced in number among CD8+ T cells at all stages of T cell development compared to Itk-single null thymi

Genotype
MGI:3771702

cx11

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt; Tg(TcraH-Y,TcrbH-Y)71Vbo/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2J

immune system

abnormal positive T cell selection ( J:31230 )

• decrease in efficiency of selection of CD4-CD8+ T3.70^hi thymocytes is observed

• number of CD4-CD8+ T cells in periphery bearing the clonotypic TCR is greatly reduced, while absolute numbers of CD4-CD8+ T cells is not different from controls

increased double-positive T cell number ( J:31230 )

• male mice show consistent increase in fraction of CD4+CD8+ thymocytes compared to controls, but total number of T cells is not different

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• number of CD4+ T cells in periphery of female mutants is reduced compared to Itk-heterozygous transgene expressing littermates

hematopoietic system

abnormal positive T cell selection ( J:31230 )

• decrease in efficiency of selection of CD4-CD8+ T3.70^hi thymocytes is observed

• number of CD4-CD8+ T cells in periphery bearing the clonotypic TCR is greatly reduced, while absolute numbers of CD4-CD8+ T cells is not different from controls

increased double-positive T cell number ( J:31230 )

• male mice show consistent increase in fraction of CD4+CD8+ thymocytes compared to controls, but total number of T cells is not different

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• number of CD4+ T cells in periphery of female mutants is reduced compared to Itk-heterozygous transgene expressing littermates

Genotype
MGI:3771701

cx12

• Allelic Composition: Itk^tm1Litt/Itk^tm1Litt; Tg(TcrAND)53Hed/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

immune system

abnormal lymphocyte morphology ( J:31230 )

• CD4+ T cells that do develop display sginficant reduction in expression of TCR alpha chain (40-50% compared to 90% in heterozygous mice littermates)

increased double-negative T cell number ( J:31230 )

• number of CD4-CD8- T cells is increased 5-7-fold compared to Itk-null mice

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• dramatic reduction in number and proportion of CD4+CD8- thymocytes is observed in thymus relative to control Itk-null mices

• profound reduction in CD4+ T cells in periphery is seen

hematopoietic system

abnormal lymphocyte morphology ( J:31230 )

• CD4+ T cells that do develop display sginficant reduction in expression of TCR alpha chain (40-50% compared to 90% in heterozygous mice littermates)

increased double-negative T cell number ( J:31230 )

• number of CD4-CD8- T cells is increased 5-7-fold compared to Itk-null mice

decreased CD4-positive, alpha-beta T cell number ( J:31230 )

• dramatic reduction in number and proportion of CD4+CD8- thymocytes is observed in thymus relative to control Itk-null mices

• profound reduction in CD4+ T cells in periphery is seen