Mouse Genome Informatics
hm
    Tbx21tm1Glm/Tbx21tm1Glm
involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
hematopoietic system
• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number
• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number
• 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
• 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
• 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
• splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type
• NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type
• NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells

immune system
• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number
• number of Ifng producing cells (Th1) decreases while Th2 cells producing Il-4 and Il-5 increase in number
• 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
• 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
• 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
• splenic NK cells from mutants produce less Ifng in response to Il-12 or Il-18 than NK cells from wild-type
• NK cells from mutants are impaired in ability to lyse YAC-1 cells compared to wild-type
• NK cells from mutants treated with poly(I:C) for activation lyse tumor cell targets equivalently to wild-type NK cells
• increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type
• 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
• increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type
• 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
• homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates
• 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
• homozygotes show peribronchial and perivenular infiltration with eosinophils and lymphocytes compared to wild-type littermates
• mice show an increase in thickness of subbasement collagen layer of the airways, with an increased numbers of bronchial myofibroblast
• 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
• increased amount of TGFb is found in bronchial alveolar lavage (BAL) fluid compared to wild-type
• 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
• increased amount of TNFa is found in bronchial alveolar lavage (BAL) fluid compared to wild-type

Mouse Models of Human Disease
OMIM IDRef(s)
Asthma, Susceptibility to 600807 J:73832