Phenotypes Associated with This Genotype

Genotype
MGI:2180789

• Allelic Composition: Tbx21^tm1Glm/Tbx21^tm1Glm
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

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

hematopoietic system

abnormal T-helper 1 cell differentiation ( J:73833 )

• differentiation of CD4 T cells into helper T cell subsets is impaired or altered; cells fail to differentiate into Th1 lineage and default to Th2 fate

decreased T helper 1 cell number ( J:73833 )

• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

increased T-helper 2 cell number ( J:73833 )

• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:73833 )

• mutants have normal numbers of Ifng-producing CD8 T cells; as well, unexpectedly, mutant CD8 T cells produce equivalent levels of Ifng to wild-type

abnormal immunoglobulin level ( J:73833 )

• normal mixed response to protein antigen immunization is altered; after TNP-KLH treatment mice produced decreased IgG2a and very slightly increased IgG1 compared to controls at day 12

abnormal NK cell physiology ( J:73833 )

• splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

impaired natural killer cell mediated cytotoxicity ( J:73833 )

• NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type

increased natural killer cell mediated cytotoxicity ( J:73833 )

• NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells

immune system

abnormal T-helper 1 cell differentiation ( J:73833 )

• differentiation of CD4 T cells into helper T cell subsets is impaired or altered; cells fail to differentiate into Th1 lineage and default to Th2 fate

decreased T helper 1 cell number ( J:73833 )

• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

increased T-helper 2 cell number ( J:73833 )

• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number

abnormal CD8-positive, alpha-beta cytotoxic T cell morphology ( J:73833 )

• mutants have normal numbers of Ifng-producing CD8 T cells; as well, unexpectedly, mutant CD8 T cells produce equivalent levels of Ifng to wild-type

abnormal immunoglobulin level ( J:73833 )

• normal mixed response to protein antigen immunization is altered; after TNP-KLH treatment mice produced decreased IgG2a and very slightly increased IgG1 compared to controls at day 12

abnormal NK cell physiology ( J:73833 )

• splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type

impaired natural killer cell mediated cytotoxicity ( J:73833 )

• NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type

increased natural killer cell mediated cytotoxicity ( J:73833 )

• NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells

abnormal cytokine level ( J:73832 )

• increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal interleukin level ( J:73832 )

• increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal tumor necrosis factor level ( J:73832 )

• increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

decreased interferon-gamma secretion ( J:73833 )

• anti-CD3 and -CD28 stimulated CD4 T cells from lymph nodes of mutants show marked decrease in Ifng (interferon-gamma) production compared to controls; in presence of Il-12, Ifng production is reduced as well

respiratory system inflammation ( J:73832 )

• homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates

increased susceptibility to parasitic infection ( J:73833 )

• mutants on C57BL/6 background produce less Ifng in response to L. major infection and fail to cure infection, similar to BALB/c (susceptible) controls, while C57BL/6 (resistant) controls cure infection

respiratory system

respiratory system inflammation ( J:73832 )

• homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates

abnormal respiratory system morphology ( J:73832 )

• mice show an increase in thickness of subbasement collagen layer of the airways, with an increased numbers of bronchial myofibroblast

increased airway responsiveness ( J:73832 )

• 4-5 week old homozygous mice exhibit airway hyperresponsiveness (AHR) to methacholine challenge, in the absence of prior immunologic sensitization; mice are more responsive without allergen challenge than wild-type mice following antigen challenge

homeostasis/metabolism

abnormal cytokine level ( J:73832 )

• increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

abnormal interleukin level ( J:73832 )

• increased amounts of Il-4 and Il-13 are found in BAL fluid; Il-5 levels are high in mutants and do not increase with allergen challenge as wild-type levels do

abnormal tumor necrosis factor level ( J:73832 )

• increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
asthma		DOID:2841	OMIM:600807	J:73832