Phenotypes associated with this allele

• Allele Symbol: Stat3^tm1Dlv
• Allele Name: targeted mutation 1, David E Levy
• Allele ID: MGI:2384272
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Stat3^tm1Dnl/Stat3^tm1Dlv	involves: C57BL/6	MGI:3028655
cn2	Stat3^tm1Dlv/Stat3^tm1Dlv Tg(Cd4-cre)1Cwi/?	involves: 129 * C57BL/6 * DBA/2	MGI:3814060
cn3	Stat3^tm1Dlv/Stat3^tm1Dlv Tg(Csf1r-icre)1Jwp/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:4429499
cn4	Stat3^tm1Dlv/Stat3^tm1Dlv Tg(MMTV-cre)4Mam/0	involves: 129P2/OlaHsd * C57BL/6J * FVB	MGI:4843432
cn5	Stat3^tm1Dlv/Stat3^tm1Dlv Tg(Cryaa-cre)10Mlr/0	involves: C57BL/6	MGI:3038248

Genotype
MGI:3028655

ht1

• Allelic Composition: Stat3^tm1Dnl/Stat3^tm1Dlv
• Genetic Background: involves: C57BL/6

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:87599 )

• 75% die within 48 hours of birth

growth/size/body

decreased body size ( J:87599 )

• mice surviving the first week of age reach only 50-60% of normal size, however by 8 weeks of age, they are only about 10% smaller than normal

decreased body weight ( J:87599 )

• body weight is 85% to 90% that of wild-type at birth

postnatal growth retardation ( J:87599 )

fetal growth retardation ( J:87599 )

• growth retardation starts during late fetal development

hematopoietic system

increased thymocyte apoptosis ( J:87599 )

decreased thymocyte number ( J:87599 )

• decrease in thymocytes number at 7 days and 6 months of age associated with increased apoptosis

immune system

increased thymocyte apoptosis ( J:87599 )

decreased thymocyte number ( J:87599 )

• decrease in thymocytes number at 7 days and 6 months of age associated with increased apoptosis

homeostasis/metabolism

abnormal circulating insulin-like growth factor I level ( J:87599 )

• decrease in serum insulin-like growth factor 1 levels at P8 and P24 but higher levels in newborns

decreased growth hormone level ( J:87599 )

• growth hormone levels at 24 days of age are reduced in males but not in females

decreased urine protein level ( J:87599 )

• decrease in major urinary protein in the urine

renal/urinary system

decreased urine protein level ( J:87599 )

• decrease in major urinary protein in the urine

cellular

increased thymocyte apoptosis ( J:87599 )

endocrine/exocrine glands

increased thymocyte apoptosis ( J:87599 )

decreased thymocyte number ( J:87599 )

• decrease in thymocytes number at 7 days and 6 months of age associated with increased apoptosis

Genotype
MGI:3814060

cn2

• Allelic Composition: Stat3^tm1Dlv/Stat3^tm1Dlv; Tg(Cd4-cre)1Cwi/?
• Genetic Background: involves: 129 * C57BL/6 * DBA/2

immune system

abnormal CD4-positive T cell differentiation ( J:124293 )

• in vitro activation of CD4 T cells with IL-6 and IL-21 pushes differentiation towards a Th1 type instead of Th17 type

• Th17 cells are absent in the lamina propia of these mice

abnormal gut-associated lymphoid tissue morphology ( J:124293 )

• Th17 cells are absent in the lamina propia of these mice

increased interferon-gamma secretion ( J:124293 )

• a large proportion of CD4 T cells produce IFN-gamma when activated in vitro with IL-6 and IL-21

decreased interleukin-17 secretion ( J:124293 )

• IL-17 is not produced by CD4 T cells in response to in vitro activation with IL-6 or IL-21 plus TGF-beta

hematopoietic system

abnormal CD4-positive T cell differentiation ( J:124293 )

• in vitro activation of CD4 T cells with IL-6 and IL-21 pushes differentiation towards a Th1 type instead of Th17 type

• Th17 cells are absent in the lamina propia of these mice

Genotype
MGI:4429499

cn3

• Allelic Composition: Stat3^tm1Dlv/Stat3^tm1Dlv; Tg(Csf1r-icre)1Jwp/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB

growth/size/body

decreased body weight ( J:156593 )

• mutant mice that do not show symptoms of colitis have significantly lower body weights at older ages compared to controls

weight loss ( J:156593 )

• observed after colitis develops

digestive/alimentary system

diarrhea ( J:156593 )

• observed after colitis develops; animals produce bloody feces

abnormal intestinal mucosa morphology ( J:156593 )

• mice with or without evident colitis show increased intestinal mucosal thickening predominantly in the proximal colon

• significant decrease in goblet cell density in inflamed colon is observed compared to controls

abnormal cecum morphology ( J:156593 )

• visible polyps are found in inflamed areas of cecum

• herniation of colonic mucosa is observed in inflamed cecum

abnormal colon morphology ( J:156593 )

• mice with or without evident colitis show increased intestinal mucosal thickening predominantly in the proximal colon

• herniation of colonic mucosa is also observed in inflamed colon

• hyperplasia and dysplasia are also exhibited in inflamed intestinal tissue with over 60% of animals showing dysplasia between 8-39 weeks of age compared to no controls showing such phenotypes

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation in the colon and reduction in mucosal thickening compared to untreated mutants

• persistent proliferation of colonic epithelium in response to inflammation is observed compared to controls, with no difference in level of cell death

• colonic epithelial differentiation is perturbed in inflamed region

colon polyps ( J:156593 )

• visible polyps are found in inflamed areas of proximal colon and cecum

• most lesions are 'flat' with a broad base or are morphologically similar to 'dysplasia-associated lesions or masses'

• polyps/lesions are tumorous

increased gastrointestinal tumor incidence ( J:156593 )

• tumors develop in proximal colon and cecum

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation and tumor development in the colon; no tumors are detected in treated animals 21-27 weeks of age

colitis ( J:156593 )

• about 20% of animals develop pronounced colitis at 8 weeks of age; by 18-20 weeks, around 50% of animals develop colitis

immune system

increased granulocyte number ( J:156593 )

• moderately increased in proximal colon in mutants

increased T cell number ( J:156593 )

• significant increase in CD3+ T cells in proximal colon

increased macrophage cell number ( J:156593 )

• mutants have significantly higher density (number) of macrophages in the proximal colon

abnormal inflammatory response ( J:156593 )

• mice have higher leukocytic infiltration scores (degree of leukocytic infiltration and increased mucosal thickness) than controls

• almost all mutants develop inflammation of the colon compared to 1 control showing increased leukocytic infiltration; leukocytic infiltration score and infiltration of macrophages and T lymphocytes are reduced in treated mutants, but infiltrated macrophage number is still much higher than in controls

colitis ( J:156593 )

• about 20% of animals develop pronounced colitis at 8 weeks of age; by 18-20 weeks, around 50% of animals develop colitis

abnormal acute inflammation ( J:156593 )

• mice with or without evident colitis show increased leukocytic infiltration compared to controls

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation in the colon

hematopoietic system

increased granulocyte number ( J:156593 )

• moderately increased in proximal colon in mutants

increased T cell number ( J:156593 )

• significant increase in CD3+ T cells in proximal colon

increased macrophage cell number ( J:156593 )

• mutants have significantly higher density (number) of macrophages in the proximal colon

neoplasm

increased gastrointestinal tumor incidence ( J:156593 )

• tumors develop in proximal colon and cecum

• mice receiving antibiotics to reduce intestinal microflora show inhibition of inflammation and tumor development in the colon; no tumors are detected in treated animals 21-27 weeks of age

increased carcinoma incidence ( J:156593 )

• carcinoma is identified in some polyps (nodules) with invasion to submucosa or muscularis external; about 16% of mutants develop carcinoma

• presence of irregular or angulated glands with cell loss, desmoplasia and multiple invading mucosa are also observed

• cells in invasive glands exhibit severe atypia with pleomorphism and basement membrane loss

behavior/neurological

decreased locomotor activity ( J:156593 )

• mutant mice that do not show symptoms of colitis are less active at older ages compared to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
colorectal cancer		DOID:9256	OMIM:114500	J:156593
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:156593

Genotype
MGI:4843432

cn4

• Allelic Composition: Stat3^tm1Dlv/Stat3^tm1Dlv; Tg(MMTV-cre)4Mam/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB

hematopoietic system

decreased T-helper 17 cell number ( J:120176 )

• reduction in the proportion of IL-17-producing T cells after polyclonally stimulated for 3 days in media alone or under optimal Th17 conditions in vitro

immune system

decreased T-helper 17 cell number ( J:120176 )

• reduction in the proportion of IL-17-producing T cells after polyclonally stimulated for 3 days in media alone or under optimal Th17 conditions in vitro

Genotype
MGI:3038248

cn5

• Allelic Composition: Stat3^tm1Dlv/Stat3^tm1Dlv; Tg(Cryaa-cre)10Mlr/0
• Genetic Background: involves: C57BL/6

vision/eye

vision/eye phenotype ( J:88422 )

N • lens development was normal