Phenotypes associated with this allele

• Allele Symbol: Gnai2^tm1Lbi
• Allele Name: targeted mutation 1, Lutz Birnbaumer
• Allele ID: MGI:2152603
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gnai2^tm1Lbi/Gnai2^tm1Lbi	129-Gnai2^tm1Lbi	MGI:3047407
hm2	Gnai2^tm1Lbi/Gnai2^tm1Lbi	B6.129S7-Gnai2^tm1Lbi	MGI:3710683
hm3	Gnai2^tm1Lbi/Gnai2^tm1Lbi	either: 129 or (involves: 129S7/SvEvBrd * C57BL/6J)	MGI:3047405
hm4	Gnai2^tm1Lbi/Gnai2^tm1Lbi	involves: 129S7/SvEvBrd	MGI:3047403
hm5	Gnai2^tm1Lbi/Gnai2^tm1Lbi	involves: 129S7/SvEvBrd * C57BL/6	MGI:4452344
hm6	Gnai2^tm1Lbi/Gnai2^tm1Lbi	involves: 129S7/SvEvBrd * C57BL/6J	MGI:3047402
cx7	Gnai2^tm1Lbi/Gnai2^tm1Lbi Tg(WTbeta2)4Wjk/0	B6.Cg-Gnai2^tm1Lbi Tg(WTbeta2)4Wjk	MGI:3799102
cx8	Gnai2^tm1Lbi/Gnai2^+ Tg(WTbeta2)4Wjk/0	B6.Cg-Gnai2^tm1Lbi Tg(WTbeta2)4Wjk	MGI:3799103
cx9	Gnai1^tm1Drs/Gnai1^tm1Drs Gnai2^tm1Lbi/Gnai2^tm1Lbi	involves: 129S7/SvEvBrd	MGI:5471657
cx10	Gnai2^tm1Lbi/Gnai2^+ Gnai3^tm1Lbi/Gnai3^tm1Lbi	involves: 129S/SvEv * 129S7/SvEvBrd	MGI:5471656

Genotype
MGI:3047407

hm1

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: 129-Gnai2^tm1Lbi

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

immune system

immune system phenotype ( J:91100 )

N • Background Sensitivity: mice on a 129X1/SvJBom genetic background do not develop colitis

abnormal cytokine secretion ( J:91100 )

• production of pro-inflammatory cytokines, TNF and IL-1beta, and the Th1 promoting cytokine IL-12p40, are increased in response to formalin-killed Saphylococcus aureus

• Background Sensitivity: superantigenic stimulation with toxic shock syndrome toxin-1 of splenocytes results in increased production of TNF and IL-1beta, but not of IL-12p40, as is seen on the mixed 129S7/SvEvBrd and C57BL/6 background

increased interleukin-1 beta secretion ( J:91100 )

• in response to formalin-killed Saphylococcus aureus and toxic shock syndrome toxin-1

increased tumor necrosis factor secretion ( J:91100 )

• in response to formalin-killed Saphylococcus aureus and toxic shock syndrome toxin-1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	inflammatory bowel disease 12	DOID:0110887	OMIM:612241	J:91100

Genotype
MGI:3710683

hm2

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: B6.129S7-Gnai2^tm1Lbi

mortality/aging

premature death ( J:125581 )

• mean survival time is 307 days compared to over 600 for control mice

growth/size/body

decreased body weight ( J:125581 )

• there is a significant drop in body weight as mice age

behavior/neurological

fatigue ( J:125581 )

• occurs in these mice as the age

digestive/alimentary system

rectal prolapse ( J:125581 )

• rectal prolapse and anal bleeding occurs in some mice as they age

chronic diarrhea ( J:125581 )

• occurs in these mice as the age

hematopoietic system

abnormal cellular extravasation ( J:120069 )

• leukocytes transgress postcapillary venules at a much slower rate in LPS exposed tissue

abnormal leukocyte adhesion ( J:120069 )

• leukocytes adhere to postcapillary venules without migrating through leading to significant accumulation

abnormal leukocyte cell number ( J:121161 )

decreased eosinophil cell number ( J:120069 )

• reduced numbers of eosinophils in airway lumen of antigen challenged mice

increased eosinophil cell number ( J:120069 )

• significant increase in peripheral blood

increased neutrophil cell number ( J:120069 )

• increase in number of neutrophils in the peripheral blood

increased lymphocyte cell number ( J:120069 )

• 2 fold increase in number of lymphocytes in the peripheral blood

increased monocyte cell number ( J:120069 )

• about 2 fold increase in number of monocytes in peripheral blood

abnormal eosinophil physiology ( J:120069 )

• eosinophil migration out of blood vessels is hindered

abnormal T cell physiology ( J:121161 )

• activated T cells show no chemotactic response in vitro to various concentrations of CXCR3 ligands CXCL9, CXCL10, or CXCL11, while wild-type cells show a weak response to CXCL9, and mount vigorous responses to CXCL10 and CXCL11; GTPgammaS membrane incorporation by mutant cells is absent in response to CXCR3 ligands

• CXCL12-evoked chemotactic responses are diminished compared to wild-type controls

• cells show similar response as controls in response to CCL19 or CCL21

immune system

abnormal cellular extravasation ( J:120069 )

• leukocytes transgress postcapillary venules at a much slower rate in LPS exposed tissue

abnormal leukocyte adhesion ( J:120069 )

• leukocytes adhere to postcapillary venules without migrating through leading to significant accumulation

abnormal leukocyte cell number ( J:121161 )

decreased eosinophil cell number ( J:120069 )

• reduced numbers of eosinophils in airway lumen of antigen challenged mice

increased eosinophil cell number ( J:120069 )

• significant increase in peripheral blood

increased neutrophil cell number ( J:120069 )

• increase in number of neutrophils in the peripheral blood

increased lymphocyte cell number ( J:120069 )

• 2 fold increase in number of lymphocytes in the peripheral blood

increased monocyte cell number ( J:120069 )

• about 2 fold increase in number of monocytes in peripheral blood

abnormal eosinophil physiology ( J:120069 )

• eosinophil migration out of blood vessels is hindered

abnormal T cell physiology ( J:121161 )

• activated T cells show no chemotactic response in vitro to various concentrations of CXCR3 ligands CXCL9, CXCL10, or CXCL11, while wild-type cells show a weak response to CXCL9, and mount vigorous responses to CXCL10 and CXCL11; GTPgammaS membrane incorporation by mutant cells is absent in response to CXCR3 ligands

• CXCL12-evoked chemotactic responses are diminished compared to wild-type controls

• cells show similar response as controls in response to CCL19 or CCL21

cellular

abnormal cellular extravasation ( J:120069 )

• leukocytes transgress postcapillary venules at a much slower rate in LPS exposed tissue

abnormal leukocyte adhesion ( J:120069 )

• leukocytes adhere to postcapillary venules without migrating through leading to significant accumulation

Genotype
MGI:3047405

hm3

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: either: 129 or (involves: 129S7/SvEvBrd * C57BL/6J)

hematopoietic system

increased thymocyte number ( J:24434 )

• increase of single positive thymocytes, evident at 2 weeks of age and preceding the onset of inflammatory bowel disease

• 3- to 5-fold increased proliferative response to T cell receptor stimuli

increased granulocyte number ( J:24434 )

• 20-fold increase in the number of granulocytes in spleens and peripheral blood

increased IgG level ( J:24434 )

• elevated in the large intestine, and more modestly in the small intestine

• correlative to increases observed in patients with inflammatory bowel disease

increased IgM level ( J:24434 )

• elevated in the large, but not small, intestine

• correlative to increases observed in patients with inflammatory bowel disease

immune system

increased thymocyte number ( J:24434 )

• increase of single positive thymocytes, evident at 2 weeks of age and preceding the onset of inflammatory bowel disease

• 3- to 5-fold increased proliferative response to T cell receptor stimuli

increased granulocyte number ( J:24434 )

• 20-fold increase in the number of granulocytes in spleens and peripheral blood

increased IgG level ( J:24434 )

• elevated in the large intestine, and more modestly in the small intestine

• correlative to increases observed in patients with inflammatory bowel disease

increased IgM level ( J:24434 )

• elevated in the large, but not small, intestine

• correlative to increases observed in patients with inflammatory bowel disease

abnormal cytokine secretion ( J:24434 )

• elevated cytokine levels produced by both thymocytes and peripheral T cells, indicating that mature thymocytes migrate properly to spleen and lymph nodes and retain a hyper-responsive cytokine production profile

endocrine/exocrine glands

increased thymocyte number ( J:24434 )

• increase of single positive thymocytes, evident at 2 weeks of age and preceding the onset of inflammatory bowel disease

• 3- to 5-fold increased proliferative response to T cell receptor stimuli

Genotype
MGI:3047403

hm4

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: involves: 129S7/SvEvBrd

mortality/aging

premature death ( J:30507 )

• mean age of death is 20 weeks

lethality during fetal growth through weaning, complete penetrance ( J:24434 )

• death sometime between E14 and 4 weeks of age

neoplasm

increased intestinal adenocarcinoma incidence ( J:24434 )

• tumors were largely confined to the large intestine with none being observed in the small intestine

digestive/alimentary system

intestinal ulcer ( J:30507 )

• with heavy chronic infiltration of lymphocytes and active plasma cells

abnormal large intestine morphology ( J:30507 )

abnormal large intestine crypts of Lieberkuhn morphology ( J:30507 )

• loss of mucus from goblet cells of crypts, atypia and loss of crypts

• glands regenerate with typical characteristics of adenocarcinomas as well as penetrating the submucosa and extending to the smooth muscle layer

abnormal colon morphology ( J:24434 , J:30507 )

• colons were irregularly dilated and had focally thickened and inflamed walls (J:24434)

• the small intestines were unaffected (J:24434)

• at necropsy walls are focally thickened (J:30507)

megacolon ( J:30507 )

• at necropsy colons are dilated

increased intestinal adenocarcinoma incidence ( J:24434 )

• tumors were largely confined to the large intestine with none being observed in the small intestine

abnormal digestive system physiology ( J:30507 )

large intestinal inflammation ( J:30507 )

• seen in 21 of 26 mice

• inflammation is restricted to the rectum and colon

• diffuse but not patchy pattern of inflammation resembles ulcerative colitis

colitis ( J:24434 )

• exhibited by all mice by 13 weeks of age

• chronic active inflammation with the distal colon being most affected

peritoneal inflammation ( J:30507 )

• serosal discoloration and increased vascularity are also observed at necropsy

• perforation and peritonitis are present at necropsy

immune system

abnormal immune system morphology ( J:30507 )

increased granulocyte number ( J:30507 )

• at 8 weeks, the spleen contain a significantly larger number of granulocytes compared to wild-type mice

increased T cell number ( J:30507 )

• 3-fold increase in CD3+ cells

increased single-positive T cell number ( J:30507 )

• 2- to 4-fold increase in single positive thymocytes

abnormal immune system physiology ( J:30507 )

increased T cell proliferation ( J:30507 )

• proliferative response to phorbol myristate acetate (PMA), staphylococcal enterotoxin A (SEA) and BABL/c(H-2^s) is increased by 3- to 5-fold

abnormal neutrophil physiology ( J:121471 )

• myeloperoxidase (MPO) levels from neutrophils are significantly lower than in wild-type at the site of infection

• however, neutrophil function is normal and serum taken from immunized mice is able to confer immunity to nae wild-type mice

increased immunoglobulin level ( J:30507 )

increased IgA level ( J:30507 )

• twice as high as in wild-type mice

increased IgG level ( J:30507 )

• twice as high as in wild-type mice

• markedly elevated in the large intestine but only modestly so in the small intestine

abnormal cytokine level ( J:121471 )

increased circulating interferon-gamma level ( J:121471 )

• IFN-gamma levels in non-immunized and immunized mice are increased compared to immunized wild-type mice

increased circulating interleukin-4 level ( J:121471 )

• IL-4 levels are significantly higher after immunization against S. stercorallis

increased circulating interleukin-5 level ( J:121471 )

• IL-5 levels are significantly higher after immunization against S. stercorallis

abnormal cytokine secretion ( J:30507 )

increased interferon-gamma secretion ( J:30507 )

• stimulated spleen and lymph node T cells and thymocytes produce several fold more INF-gamma

increased interleukin-2 secretion ( J:30507 )

• stimulated spleen and lymph node T cells and thymocytes produce several fold more IL-2

• however, IL-4 production from stimulated spleen and lymph node T cells and thymocytes is only modestly enhanced if at all

increased tumor necrosis factor secretion ( J:30507 )

• stimulated spleen and lymph node T cells and thymocytes produce several fold more TNF

increased inflammatory response ( J:30507 )

large intestinal inflammation ( J:30507 )

• seen in 21 of 26 mice

• inflammation is restricted to the rectum and colon

• diffuse but not patchy pattern of inflammation resembles ulcerative colitis

colitis ( J:24434 )

• exhibited by all mice by 13 weeks of age

• chronic active inflammation with the distal colon being most affected

peritoneal inflammation ( J:30507 )

• serosal discoloration and increased vascularity are also observed at necropsy

• perforation and peritonitis are present at necropsy

increased susceptibility to parasitic infection ( J:121471 )

• following immunization and exposure to S. stercorallis, mice have decreased larval killing of 37% compared to 91% in wild-type mice

• IL-4 and IL-5 levels are significantly higher after immunization against S. stercorallis

• fewer neutrophils, eosinophils, macrophages, and lymphocytes are recruited into the site of infection

• myeloperoxidase (MPO) levels from neutrophils are significantly lower than in wild-type at the site of infection

• however, serum taken from immunized mice is able to confer immunity to nae wild-type mice

growth/size/body

decreased body weight ( J:30507 )

• at 6 weeks, mice gain weight slower

weight loss ( J:30507 )

postnatal growth retardation ( J:30507 )

• at 6 weeks, mice gain weight slower

homeostasis/metabolism

abnormal cytokine level ( J:121471 )

increased circulating interferon-gamma level ( J:121471 )

• IFN-gamma levels in non-immunized and immunized mice are increased compared to immunized wild-type mice

increased circulating interleukin-4 level ( J:121471 )

• IL-4 levels are significantly higher after immunization against S. stercorallis

increased circulating interleukin-5 level ( J:121471 )

• IL-5 levels are significantly higher after immunization against S. stercorallis

abnormal response/metabolism to endogenous compounds ( J:30507 )

• response to prostoglandin E and nicotinic acid is blunted about 50%

decreased physiological sensitivity to xenobiotic ( J:30507 )

• inhibition of adenylyl cyclase in response to phenylisopropyl adenosine or carbachol is blunted about 50%

increased physiological sensitivity to xenobiotic ( J:30507 )

• proliferative response to phorbol myristate acetate (PMA), staphylococcal enterotoxin A (SEA) and BABL/c(H-2^s) is increased by 3- to 5-fold

hematopoietic system

increased T cell proliferation ( J:30507 )

• proliferative response to phorbol myristate acetate (PMA), staphylococcal enterotoxin A (SEA) and BABL/c(H-2^s) is increased by 3- to 5-fold

increased granulocyte number ( J:30507 )

• at 8 weeks, the spleen contain a significantly larger number of granulocytes compared to wild-type mice

increased T cell number ( J:30507 )

• 3-fold increase in CD3+ cells

increased single-positive T cell number ( J:30507 )

• 2- to 4-fold increase in single positive thymocytes

abnormal neutrophil physiology ( J:121471 )

• myeloperoxidase (MPO) levels from neutrophils are significantly lower than in wild-type at the site of infection

• however, neutrophil function is normal and serum taken from immunized mice is able to confer immunity to nae wild-type mice

increased immunoglobulin level ( J:30507 )

increased IgA level ( J:30507 )

• twice as high as in wild-type mice

increased IgG level ( J:30507 )

• twice as high as in wild-type mice

• markedly elevated in the large intestine but only modestly so in the small intestine

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:30507 )

• loss of mucus from goblet cells of crypts, atypia and loss of crypts

• glands regenerate with typical characteristics of adenocarcinomas as well as penetrating the submucosa and extending to the smooth muscle layer

cellular

increased T cell proliferation ( J:30507 )

• proliferative response to phorbol myristate acetate (PMA), staphylococcal enterotoxin A (SEA) and BABL/c(H-2^s) is increased by 3- to 5-fold

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease 12		DOID:0110887	OMIM:612241	J:24434 , J:30507

Genotype
MGI:4452344

hm5

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

digestive/alimentary system

colitis ( J:91100 )

• Background Sensitivity: mutants on a mixed 129S7/SvEvBrd and C57BL/6 genetic background develop colitis between 12-25 weeks of age, resembling human ulcerative colitis

immune system

colitis ( J:91100 )

• Background Sensitivity: mutants on a mixed 129S7/SvEvBrd and C57BL/6 genetic background develop colitis between 12-25 weeks of age, resembling human ulcerative colitis

abnormal cytokine secretion ( J:91100 )

• production of pro-inflammatory cytokines, TNF and IL-1beta, and the Th1 promoting cytokine IL-12p40, are increased in response to formalin-killed Saphylococcus aureus and in response to superantigen stimulation via toxic shock syndrome toxin-1

increased interleukin-1 beta secretion ( J:91100 )

• in response to formalin-killed Saphylococcus aureus and toxic shock syndrome toxin-1

increased tumor necrosis factor secretion ( J:91100 )

• in response to formalin-killed Saphylococcus aureus and toxic shock syndrome toxin-1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease 12		DOID:0110887	OMIM:612241	J:91100

Genotype
MGI:3047402

hm6

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J

mortality/aging

premature death ( J:24434 )

• the mean age of spontaneous death was 21 weeks

• 75% had died by 36 weeks of age

postnatal lethality, incomplete penetrance ( J:24434 )

• death sometime between E14 and 4 weeks of age

neoplasm

increased intestinal adenocarcinoma incidence ( J:24434 )

• tumors were largely confined to the large intestine with none being observed in the small intestine

digestive/alimentary system

abnormal colon morphology ( J:24434 )

• colons were irregularly dilated and had focally thickened and inflamed walls

• the small intestines were unaffected

increased intestinal adenocarcinoma incidence ( J:24434 )

• tumors were largely confined to the large intestine with none being observed in the small intestine

colitis ( J:24434 )

• exhibited by all mice by 13 weeks of age

• chronic active inflammation with the distal colon being most affected

growth/size/body

decreased body weight ( J:24434 )

• weight decreased by 20% to 30% prior to death

postnatal growth retardation ( J:24434 )

immune system

colitis ( J:24434 )

• exhibited by all mice by 13 weeks of age

• chronic active inflammation with the distal colon being most affected

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease 12		DOID:0110887	OMIM:612241	J:24434

Genotype
MGI:3799102

cx7

• Allelic Composition: Gnai2^tm1Lbi/Gnai2^tm1Lbi; Tg(WTbeta2)4Wjk/0
• Genetic Background: B6.Cg-Gnai2^tm1Lbi Tg(WTbeta2)4Wjk

mortality/aging

postnatal lethality, complete penetrance ( J:125581 )

• all pups die between 1 and 4 days after birth

embryonic lethality, incomplete penetrance ( J:125581 )

• less then half of the expected Mendelian distribution for pups of this genotype are present at birth

growth/size/body

decreased birth body size ( J:125581 )

• pups are smaller than littermate controls at birth

behavior/neurological

weakness ( J:125581 )

• pups are weaker than littermate controls at birth

cardiovascular system

dilated heart ( J:125581 )

• dilated hearts are found at necropsy of mice that die shortly after birth

Genotype
MGI:3799103

cx8

• Allelic Composition: Gnai2^tm1Lbi/Gnai2⁺; Tg(WTbeta2)4Wjk/0
• Genetic Background: B6.Cg-Gnai2^tm1Lbi Tg(WTbeta2)4Wjk

mortality/aging

premature death ( J:125581 )

• mean survival time is 223 days compared to over 600 for control mice and most mice die by 1 year of age

behavior/neurological

fatigue ( J:125581 )

• fatigue occurs in mice with age

cardiovascular system

increased heart weight ( J:125581 )

• the heart to body weight ratio is about twice that of control mice at 7 months of age

dilated heart ( J:125581 )

• heart appears dilated at necropsy

homeostasis/metabolism

cyanosis ( J:125581 )

• occurs in mucosal membranes with age

pulmonary edema ( J:125581 )

• often found at necropsy

ascites ( J:125581 )

• often found at necropsy

liver/biliary system

abnormal liver morphology ( J:125581 )

• liver congestion is often found at necropsy

respiratory system

pulmonary edema ( J:125581 )

• often found at necropsy

respiratory distress ( J:125581 )

• occurs in mice with age

growth/size/body

increased heart weight ( J:125581 )

• the heart to body weight ratio is about twice that of control mice at 7 months of age

Genotype
MGI:5471657

cx9

• Allelic Composition: Gnai1^tm1Drs/Gnai1^tm1Drs; Gnai2^tm1Lbi/Gnai2^tm1Lbi
• Genetic Background: involves: 129S7/SvEvBrd

Rib and sternum defects in mice with mutations of Gnai1, Gnai2, and/or Gnai3

skeleton

skeleton phenotype ( J:193170 )

N • no rib fusions are detected

abnormal sternocostal joint morphology ( J:193170 )

• one mouse has the eighth rib ectopically attached to the sternum

Genotype
MGI:5471656

cx10

• Allelic Composition: Gnai2^tm1Lbi/Gnai2⁺; Gnai3^tm1Lbi/Gnai3^tm1Lbi
• Genetic Background: involves: 129S/SvEv * 129S7/SvEvBrd

Rib and sternum defects in mice with mutations of Gnai1, Gnai2, and/or Gnai3

skeleton

abnormal sternocostal joint morphology ( J:193170 )

• one mouse has the eighth rib ectopically attached to the sternum

rib fusion ( J:193170 )

• rib fusions are similar in severity to mice homozygous for Gnai3^tm1Lbi and Gnai1^tm1Drs