Phenotypes associated with this allele

• Allele Symbol: Tg(H2-K-Fosl2,-EGFP)13Wag
• Allele Name: transgene insertion 13, Erwin F Wagner
• Allele ID: MGI:3813493
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(Acta2-cre/ERT2)#Pcn/0 Tgfbr2^tm1Karl/Tgfbr2^tm1Karl Tg(H2-K-Fosl2,-EGFP)13Wag/0	B6.Cg-Tgfbr2^tm1Karl Tg(Acta2-cre/ERT2)#Pcn Tg(H2-K-Fosl2,-EGFP)13Wag	MGI:5927438
tg2	Tg(H2-K-Fosl2,-EGFP)13Wag/0	B6.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag	MGI:5927436
tg3	Tg(H2-K-Fosl2,-EGFP)13Wag/0	either: 129.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag or B6.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag	MGI:3813506

Genotype
MGI:5927438

cn1

• Allelic Composition: Tg(Acta2-cre/ERT2)#Pcn/0; Tgfbr2^tm1Karl/Tgfbr2^tm1Karl; Tg(H2-K-Fosl2,-EGFP)13Wag/0
• Genetic Background: B6.Cg-Tgfbr2^tm1Karl Tg(Acta2-cre/ERT2)#Pcn Tg(H2-K-Fosl2,-EGFP)13Wag

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

respiratory system

lung inflammation ( J:238723 )

• mice treated with tamoxifen show similar lung inflammation as single Tg(H2-K-Fosl2,EGFP)13Wag mice

pulmonary fibrosis ( J:238723 )

• mice treated with tamoxifen show similar pulmonary fibrosis as single Tg(H2-K-Fosl2,EGFP)13Wag mice

immune system

lung inflammation ( J:238723 )

• mice treated with tamoxifen show similar lung inflammation as single Tg(H2-K-Fosl2,EGFP)13Wag mice

cardiovascular system

cardiovascular system phenotype ( J:238723 )

N • mice treated with tamoxifen show diminished expansion of the smooth muscle cell area in pulmonary arteries and reduced proliferation of pulmonary artery smooth muscle cells that is seen in single Tg(H2-K-Fosl2,EGFP)13Wag mice

Genotype
MGI:5927436

tg2

• Allelic Composition: Tg(H2-K-Fosl2,-EGFP)13Wag/0
• Genetic Background: B6.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag

respiratory system

abnormal lung vasculature morphology ( J:238723 )

• beginning at 10 weeks of age, mice develop pulmonary arterial vascular remodeling, characterized by increased wall thickness and narrowing of the arterial lumen

• mice treated with the pan-TGFbeta-neutralizing monoclonal antibody 1D11 show amelioration of the pulmonary vascular remodeling

lung inflammation ( J:238723 )

• mice develop pulmonary inflammation, most prominently around the distal vasculature and airways starting at 6-10 weeks of age, with increases in macrophages, lymphocytes, and especially, granulocytes in BAL fluid

• pulmonary fibrosis is prominent in the perivascular area but also seen in the peripheral, subpleural lung

• mice treated with the pan-TGFbeta-neutralizing monoclonal antibody 1D11 show increased severity of lung inflammation

pulmonary fibrosis ( J:238723 )

• mice develop pulmonary fibrosis that becomes prominent by 14 weeks of age

• hydroxyproline content in the lungs is increased at 14 weeks of age

• treatment with the pan-TGFbeta-neutralizing monoclonal antibody 1D11 has no effect on pulmonary fibrosis

cardiovascular system

abnormal lung vasculature morphology ( J:238723 )

• beginning at 10 weeks of age, mice develop pulmonary arterial vascular remodeling, characterized by increased wall thickness and narrowing of the arterial lumen

• mice treated with the pan-TGFbeta-neutralizing monoclonal antibody 1D11 show amelioration of the pulmonary vascular remodeling

vascular smooth muscle hyperplasia ( J:238723 )

• expansion of the vascular smooth muscle compartment in peripheral pulmonary arteries of lungs

• increase in the proportion of Ki67-positive smooth muscle cells in the lungs, indicating increased proliferation

immune system

lung inflammation ( J:238723 )

• mice develop pulmonary inflammation, most prominently around the distal vasculature and airways starting at 6-10 weeks of age, with increases in macrophages, lymphocytes, and especially, granulocytes in BAL fluid

• pulmonary fibrosis is prominent in the perivascular area but also seen in the peripheral, subpleural lung

• mice treated with the pan-TGFbeta-neutralizing monoclonal antibody 1D11 show increased severity of lung inflammation

muscle

vascular smooth muscle hyperplasia ( J:238723 )

• expansion of the vascular smooth muscle compartment in peripheral pulmonary arteries of lungs

• increase in the proportion of Ki67-positive smooth muscle cells in the lungs, indicating increased proliferation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
systemic scleroderma		DOID:418	OMIM:181750	J:238723

Genotype
MGI:3813506

tg3

• Allelic Composition: Tg(H2-K-Fosl2,-EGFP)13Wag/0
• Genetic Background: either: 129.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag or B6.Cg-Tg(H2-K-Fosl2,-EGFP)13Wag

mortality/aging

premature death ( J:139032 )

• mice die at 17 weeks of age with signs of respiratory distress

respiratory system

abnormal lung morphology ( J:139032 )

• at 17 weeks, mice exhibit pulmonary tissue stiffness

• end stage lungs exhibit fibrosis, dense lymphoid infiltration, hyperplasia of bronchus-associated lymphoid tissue and honeycombing of the peripheral lung lobules

increased lung weight ( J:139032 )

• at 17 weeks

pulmonary fibrosis ( J:139032 )

• mice exhibit secondary lung fibrosis that is preceded by pulmonary artery obliteration

• reconstituting mice with wild-type bone marrow or crossing mice to a Rag2 null background do not prevent fibrosis

• mice exhibit an increase in osteopontin, IL-2, IL-4, IL-6 and GM-CSF in the lungs with terminal staged lungs also expressing IL-1beta, IFN-gamma, CCL1, CCL2, CCL3, CCL4, CXCL2, CXCL10 and CXCL11

• however, lung fibrosis is not preceded by apoptosis

tachypnea ( J:139032 )

respiratory distress ( J:139032 )

• at 17 weeks mice exhibit signs of respiratory distress such as tachypnea and hunched posture

cardiovascular system

abnormal pulmonary artery morphology ( J:139032 )

• at 12 weeks, the pulmonary artery walls exhibit increased thickness compared to in wild-type mice

• obliteration of the pulmonary arteries, consisting of neointima formation induced by proliferation of vascular smooth muscle cells, coincides with perivascular inflammation

cardiac fibrosis ( J:139032 )

• mice exhibit fibrosis in the heart

skeleton

increased bone mass ( J:139032 )

behavior/neurological

hunched posture ( J:139032 )

neoplasm

increased fibrosarcoma incidence ( J:139032 )

• rarely

integument

skin fibrosis ( J:139032 )

• mice exhibit fibrosis in the skin

liver/biliary system

liver fibrosis ( J:139032 )

• mice exhibit fibrosis in the periportal tracts of the liver

renal/urinary system

renal/urinary system phenotype ( J:139032 )

N • no fibrosis is observed in the kidney

endocrine/exocrine glands

thymus fibrosis ( J:139032 )

• mice exhibit fibrosis in the thymus

hematopoietic system

thymus fibrosis ( J:139032 )

• mice exhibit fibrosis in the thymus

immune system

thymus fibrosis ( J:139032 )

• mice exhibit fibrosis in the thymus

digestive/alimentary system

esophagus fibrosis ( J:139032 )

• mice exhibit fibrosis in the esophagus

stomach fibrosis ( J:139032 )

• mice exhibit fibrosis in the stomach

growth/size/body

increased lung weight ( J:139032 )

• at 17 weeks

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic pulmonary fibrosis		DOID:0050156	OMIM:178500	J:139032