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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Tbx21tm1Glm
targeted mutation 1, Laurie H Glimcher
MGI:2180194
Summary 10 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
 		Tbx21tm1Glm/Tbx21tm1Glm B6.129S6-Tbx21tm1Glm MGI:3830297
hm2
 		Tbx21tm1Glm/Tbx21tm1Glm C.129S6-Tbx21tm1Glm/J MGI:3662847
hm3
 		Tbx21tm1Glm/Tbx21tm1Glm involves: 129S6/SvEvTac MGI:3851531
hm4
 		Tbx21tm1Glm/Tbx21tm1Glm involves: 129S6/SvEvTac * C57BL/6 MGI:2180789
ht5
 		Tbx21tm1Glm/Tbx21+ involves: 129S6/SvEvTac * C57BL/6 MGI:2180790
cn6
 		Eomestm1.1Bflu/Eomestm1.1Bflu
Tbx21tm1Glm/Tbx21tm1Glm
Tg(Cd4-cre)1Cwi/0 		involves: 129S6/SvEvTac * C57BL/6 * DBA/2 * SJL MGI:4830339
cx7
 		Ldlrtm1Her/Ldlrtm1Her
Tbx21tm1Glm/Tbx21tm1Glm 		involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6 MGI:3719026
cx8
 		Tbx21tm1Glm/Tbx21tm1Glm
Tg(TRAMP)8247Ng/0 		involves: 129S6/SvEvTac * C57BL/6 MGI:3662841
cx9
 		Eomestm1.1Twa/?
Tbx21tm1Glm/Tbx21tm1Glm 		involves: 129S6/SvEvTac * C57BL/6N MGI:5699431
cx10
 		Rag2tm1Fwa/Rag2tm1Fwa
Tbx21tm1Glm/Tbx21tm1Glm 		involves: 129S/SvEv * 129S6/SvEvTac MGI:4360989


Genotype
MGI:3830297
hm1
Allelic
Composition		 Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 B6.129S6-Tbx21tm1Glm
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal CD4-positive T cell differentiation ( J:143729 )
• wild-type CD4+ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12
• mutant polarized Th17 CD4+ T cells fail to convert to the Th1-like state in the presence of IL-12

hematopoietic system
abnormal CD4-positive T cell differentiation ( J:143729 )
• wild-type CD4+ T cells polarized under Th17 conditions can be converted to a Th1-like cells (i.e. they express IFN-gamma) by culturing with IL-12
• mutant polarized Th17 CD4+ T cells fail to convert to the Th1-like state in the presence of IL-12




Genotype
MGI:3662847
hm2
Allelic
Composition		 Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 C.129S6-Tbx21tm1Glm/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal CD4-positive, alpha-beta T cell physiology ( J:111932 )
• primed splenocytes from deficient animals produce less interferon-gamma (Ifng) than wild-type cells, but produce much increased levels of Il-10 throughout the course of the disease compared to wild-type
• however, recall responses of in vivo primed splenocytes from mutants 10 days after immunization are comparable to wild-type as significant proliferation in response to PLP peptide is observed ex vivo
abnormal cytokine secretion ( J:111932 )
• wild-type mice show presence of Ifng in the spinal cord after disease development, while mutants show no Ifng but significant 1l-10 production
decreased susceptibility to experimental autoimmune encephalomyelitis ( J:111932 )
• when immunized with PLP (proteolipid protein) peptide 180-199, mutants are resistant to development of clinical experimental autoimmune encephalitis (EAE) disease while wild-type littermates develop a more severe form of disease
• Tbx21-deficient mice show a lower incidence of EAE over a period of 40 days vs wild-type controls
• mutants have a very mild clinical course of disease whereas wild-type show an earlier onset and develop a higher disease grade (2.5 vs 1.25)
• upon adoptive transfer of wild-type PLP-specific T cells, mutants show decreased EAE severity compared to wild-type
CNS inflammation ( J:111932 )
• CNS of mutants show less infiltration of leukocytes into the spinal cord at 5 days after EAE onset (15 days); very little CD4+ T cell infiltration is seen compared to wild-type spinal cords

nervous system
CNS inflammation ( J:111932 )
• CNS of mutants show less infiltration of leukocytes into the spinal cord at 5 days after EAE onset (15 days); very little CD4+ T cell infiltration is seen compared to wild-type spinal cords

hematopoietic system
abnormal CD4-positive, alpha-beta T cell physiology ( J:111932 )
• primed splenocytes from deficient animals produce less interferon-gamma (Ifng) than wild-type cells, but produce much increased levels of Il-10 throughout the course of the disease compared to wild-type
• however, recall responses of in vivo primed splenocytes from mutants 10 days after immunization are comparable to wild-type as significant proliferation in response to PLP peptide is observed ex vivo




Genotype
MGI:3851531
hm3
Allelic
Composition		 Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 involves: 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 show a modest decrease in migration to CXCL10
increased susceptibility to induced colitis ( J:141481 )
• DSS-treated mice develop more extensive and severe inflammatory infiltrate, edema, extensive ulceration, and crypt loss compared with similarly treated wild-type mice
abnormal cytokine level ( J:112600 )
• T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more interferon gamma (Ifng) and Ifng-secreting cells than wild-type ; numbers of IL-17a producing cells as well as IL-17a levels are higher than in wild-type
increased interleukin-17 secretion ( J:163822 )
• when CD8+ T cells are cultured in Th17-polarizing conditions 2-3 fold more IL17 producing cells are produced

homeostasis/metabolism
abnormal cytokine level ( J:112600 )
• T cells from mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide show more interferon gamma (Ifng) and Ifng-secreting cells than wild-type ; numbers of IL-17a producing cells as well as IL-17a levels are higher than in wild-type

digestive/alimentary system
increased susceptibility to induced colitis ( J:141481 )
• DSS-treated mice develop more extensive and severe inflammatory infiltrate, edema, extensive ulceration, and crypt loss compared with similarly treated wild-type mice

hematopoietic system
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 show a modest decrease in migration to CXCL10

cellular
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 show a modest decrease in migration to CXCL10




Genotype
MGI:2180789
hm4
Allelic
Composition		 Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ 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




Genotype
MGI:2180790
ht5
Allelic
Composition		 Tbx21tm1Glm/Tbx21+
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
decreased T helper 1 cell number ( J:73833 )
• only 42% of CD4 T cells produce high levels of Ifng compared to wild-type
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

immune system
decreased T helper 1 cell number ( J:73833 )
• only 42% of CD4 T cells produce high levels of Ifng compared to wild-type
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
abnormal cytokine level ( J:73833 )
• 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

respiratory system
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:73833 )
• 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




Genotype
MGI:4830339
cn6
Allelic
Composition		 Eomestm1.1Bflu/Eomestm1.1Bflu
Tbx21tm1Glm/Tbx21tm1Glm
Tg(Cd4-cre)1Cwi/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6 * DBA/2 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eomestm1.1Bflu mutation (1 available); any Eomes mutation (41 available)
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
Tg(Cd4-cre)1Cwi mutation (10 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 cells show a total lack of migration toward CXCL10
decreased memory T cell number ( J:163822 )
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells

immune system
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 cells show a total lack of migration toward CXCL10
decreased memory T cell number ( J:163822 )
• CD44+ effector/memory T cells are reduced in both CD4+ and CD8+ T cells
decreased interferon-gamma secretion ( J:163822 )
• by CD8 cells cultured for 4 days under Th1 conditions
increased interleukin-17 secretion ( J:163822 )
• when CD8+ T cells are cultured in Th17-polarizing conditions 3 fold more IL17 producing cells are produced
increased interleukin-4 secretion ( J:163822 )
• when CD8+ T cells are cultured in Tc2-polarizing conditions 3 fold more IL4 producing cells are produced

neoplasm
increased tumor incidence ( J:163822 )
• 60% of mice vaccinated against B16 melenoma still grow tumors upon B16 injection

cellular
abnormal leukocyte migration ( J:163822 )
• Th1 and Tc1 cells show a total lack of migration toward CXCL10




Genotype
MGI:3719026
cx7
Allelic
Composition		 Ldlrtm1Her/Ldlrtm1Her
Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 involves: 129S6/SvEvTac * 129S7/SvEvBrd * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ldlrtm1Her mutation (19 available); any Ldlr mutation (76 available)
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype

Phenotype of aortic arch atherosclerotic lesions in Tbx21tm1Glm/Tbx21tm1Glm Ldlrtm1Her/Ldlrtm1Her and Ldlrtm1Her/Ldlrtm1Her mice

cardiovascular system
abnormal susceptibility to atherosclerosis ( J:96110 )
• atherosclerosis in both aortic arch and descending aorta is significantly reduced compared with Ldlrtm1Her homozygotes and lesions have less smooth muscle content
• males have an 81% reduction in the aortic arch intimal area of lesions and 49% reduction in descending aorta compared with control males, however no differences seen in females
• after 8 weeks of proatherogenic diet, intimal smooth muscle cell content is lower in aortic arch than in controls, indicating a delay in evolution of lesions

homeostasis/metabolism
increased circulating cholesterol level ( J:96110 )
• hypercholesterolemic; cholesterol levels are no different from those in Ldlrtm1Her homozygotes

immune system
decreased IgG level ( J:96110 )
• significant reduction of total IgG2a compared to Ldlrtm1Her homozygotes; IgG2a titers to both MDA-LDL and CuOx-LDL are reduced or absent
• IgG1 titers to both antigens (MDA-LDL and CuOx-LDL) are reduced despite similar total levels of IgG1
increased IgM level ( J:96110 )
• exhibit a more than 2.5-fold increase in the titer of atheroprotective E06 natural IgM antibodies compared to Ldlrtm1Her homozygotes
decreased interferon-gamma secretion ( J:96110 )
• unlike CD4+ T cells in Ldlrtm1Her homozygotes on a high cholesterol diet, T cells do not produce significant amounts of IFN-gamma upon polyclonal stimulation with anti-CD3 and upon stimulation with plaque antigen hsp60
abnormal interleukin secretion ( J:96110 )
• on a high cholesterol diet, higher levels of IL-4, IL-5, and IL-10 are produced upon anti-CD3 stimulation and higher levels of IL-5 and IL-10 upon hsp60 stimulation of T cells compared to T cells from Ldlrtm1Her homozygotes

hematopoietic system
decreased IgG level ( J:96110 )
• significant reduction of total IgG2a compared to Ldlrtm1Her homozygotes; IgG2a titers to both MDA-LDL and CuOx-LDL are reduced or absent
• IgG1 titers to both antigens (MDA-LDL and CuOx-LDL) are reduced despite similar total levels of IgG1
increased IgM level ( J:96110 )
• exhibit a more than 2.5-fold increase in the titer of atheroprotective E06 natural IgM antibodies compared to Ldlrtm1Her homozygotes




Genotype
MGI:3662841
cx8
Allelic
Composition		 Tbx21tm1Glm/Tbx21tm1Glm
Tg(TRAMP)8247Ng/0
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
Tg(TRAMP)8247Ng mutation (1 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
neoplasm
increased prostate gland tumor incidence ( J:88093 )
• mice aged 21-30 weeks of age develop primary prostate cancers; frequency is comparable to Tbx21-sufficient transgenic mice
• all mice regardless of Tbx21 status develop high-grade prostatic epithelial neoplasia with 96% of Tbx21-sufficient vs 91% of Tbx21-deficient transgenic mice developing overt adenocarcinoma
• Tbx21-deficient transgenics develop a modest but somewhat higher grade adenocarcinomas than Tbx21-sufficient mice
• overall tumor size does not differ significantly between genotypes
increased metastatic potential ( J:88093 )
• Tbx21-deficient transgenic mice consistently develop increased frequency of metastatic disease in the liver, lung or salivary glands (3/21 Tbx21-sufficient vs 13/25 Tbx21-null transgenics)
• per organ, tissues develop higher rates of metastasis(24% of 88 organs) vs Tbx21-sufficient transgenic mice (6% of 79 organs); metastasis is not seen in non-transgenic Tbx21-sufficient animals but was observed in 1 non-transgenic Tbx21-null mouse with low grade prostatic adenocarcinoma

reproductive system
increased prostate gland tumor incidence ( J:88093 )
• mice aged 21-30 weeks of age develop primary prostate cancers; frequency is comparable to Tbx21-sufficient transgenic mice
• all mice regardless of Tbx21 status develop high-grade prostatic epithelial neoplasia with 96% of Tbx21-sufficient vs 91% of Tbx21-deficient transgenic mice developing overt adenocarcinoma
• Tbx21-deficient transgenics develop a modest but somewhat higher grade adenocarcinomas than Tbx21-sufficient mice
• overall tumor size does not differ significantly between genotypes

endocrine/exocrine glands
increased prostate gland tumor incidence ( J:88093 )
• mice aged 21-30 weeks of age develop primary prostate cancers; frequency is comparable to Tbx21-sufficient transgenic mice
• all mice regardless of Tbx21 status develop high-grade prostatic epithelial neoplasia with 96% of Tbx21-sufficient vs 91% of Tbx21-deficient transgenic mice developing overt adenocarcinoma
• Tbx21-deficient transgenics develop a modest but somewhat higher grade adenocarcinomas than Tbx21-sufficient mice
• overall tumor size does not differ significantly between genotypes




Genotype
MGI:5699431
cx9
Allelic
Composition		 Eomestm1.1Twa/?
Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 involves: 129S6/SvEvTac * C57BL/6N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eomestm1.1Twa mutation (1 available); any Eomes mutation (41 available)
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
immune system
abnormal NK cell differentiation ( J:210160 )
• Eomes- NK cells are lacking

hematopoietic system
abnormal NK cell differentiation ( J:210160 )
• Eomes- NK cells are lacking




Genotype
MGI:4360989
cx10
Allelic
Composition		 Rag2tm1Fwa/Rag2tm1Fwa
Tbx21tm1Glm/Tbx21tm1Glm
Genetic
Background		 involves: 129S/SvEv * 129S6/SvEvTac
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rag2tm1Fwa mutation (48 available); any Rag2 mutation (117 available)
Tbx21tm1Glm mutation (2 available); any Tbx21 mutation (36 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
digestive/alimentary system
digestive/alimentary phenotype ( J:141481 )
N
• despite developing spontaneous ulcerative colitis, mice exhibit normal stomachs and small intestines
abnormal intestinal epithelium morphology ( J:141481 )
• at 3.5 weeks, mice exhibit large epithelial discontinuities with a 4- to 5-fold increase in apoptosis of epithelial cells compared with wild-type or single homozygous mice
• however, treatment with anti-TNF-alpha antibodies normalizes the level of apoptosis
abnormal large intestine crypts of Lieberkuhn morphology ( J:141481 )
• mice exhibit crypt loss associated with the development of colitis
rectal prolapse ( J:141481 )
• mice exhibit anorectal prolapse unlike wild-type or single homozygous mice
abnormal digestive system physiology ( J:141481 )
• at 3.5 weeks, colonic epithelial barrier is 2-fold more permeable than in Rag2tm1Fwa homozygotes
• at 4 to 5 weeks, colonic epithelial barrier is increased 3-fold
• at 5 to 6 weeks, colonic epithelial barrier is increased 8.6-fold
large intestinal inflammation ( J:141481 )
• by 4 weeks, mice develop inflammation of the rectum and left colon unlike or single homozygous wild-type mice
colitis ( J:141481 )
• mice exhibit inflammatory infiltrate in the lamina propria, neutrophil infiltration of the crypt and surface epithelium, and epithelial injury with surface denudations and ulcerations associated with crypt loss and epithelial mucodepletion
• by 4 weeks of age, mice develop highly penetrant and severe colitis unlike wild-type or single homozygous mice that increases in severity over time
• at 8 weeks, mice exhibit marked inflammation and colonic thickening unlike Rag2tm1Fwa homozygotes
• however, treatment with anti-TNF-alpha antibodies, T regulatory cells, or broad spectrum antibiotics restores normal colon phenotype, and treatment with broad spectrum antibiotics prevents communication of colitis to offspring
• female mice cross-fostering wild-type mice and Rag2tm1Fwa homozygotes fail to establish normal resistance to colitis in cross-fostered pups and mice can transmit susceptibility to colitis to wild-type mice housemates

immune system
large intestinal inflammation ( J:141481 )
• by 4 weeks, mice develop inflammation of the rectum and left colon unlike or single homozygous wild-type mice
colitis ( J:141481 )
• mice exhibit inflammatory infiltrate in the lamina propria, neutrophil infiltration of the crypt and surface epithelium, and epithelial injury with surface denudations and ulcerations associated with crypt loss and epithelial mucodepletion
• by 4 weeks of age, mice develop highly penetrant and severe colitis unlike wild-type or single homozygous mice that increases in severity over time
• at 8 weeks, mice exhibit marked inflammation and colonic thickening unlike Rag2tm1Fwa homozygotes
• however, treatment with anti-TNF-alpha antibodies, T regulatory cells, or broad spectrum antibiotics restores normal colon phenotype, and treatment with broad spectrum antibiotics prevents communication of colitis to offspring
• female mice cross-fostering wild-type mice and Rag2tm1Fwa homozygotes fail to establish normal resistance to colitis in cross-fostered pups and mice can transmit susceptibility to colitis to wild-type mice housemates
increased tumor necrosis factor secretion ( J:141481 )
• as early as 2 weeks, colonic dendritic cells produce more TNF-alpha than wild-type cells
• in culture, bone marrow-derived dendritic cells produce more TNF-alpha compared with wild-type cells
• however, treatment with T regulatory cells reduced TNF-alpha levels

endocrine/exocrine glands
abnormal large intestine crypts of Lieberkuhn morphology ( J:141481 )
• mice exhibit crypt loss associated with the development of colitis

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
ulcerative colitis DOID:8577 J:141481




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04/16/2024
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