Phenotypes associated with this allele

• Allele Symbol: Tnfrsf1b^tm1.1Gkl
• Allele Name: targeted mutation 1.1, George Kollias
• Allele ID: MGI:6195552
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tnf^tm2Gkl/Tnf^+ Tnfrsf1b^tm1.1Gkl/Tnfrsf1b^tm1.1Gkl Tg(Col6a1-cre)1Gkl/0	involves: 129S/SvEv * C57BL/6 * C57BL/6J * CBA	MGI:6195612
cn2	Tnfrsf1b^tm1.1Gkl/Tnfrsf1b^tm1.1Gkl Tg(Col6a1-cre)1Gkl/0	involves: C57BL/6 * C57BL/6J * CBA	MGI:6195560

Genotype
MGI:6195612

cn1

• Allelic Composition: Tnf^tm2Gkl/Tnf⁺; Tnfrsf1b^tm1.1Gkl/Tnfrsf1b^tm1.1Gkl; Tg(Col6a1-cre)1Gkl/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * C57BL/6J * CBA

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

cardiovascular system

cardiovascular system phenotype ( J:264147 )

N • mice show amelioration of the aortic valve stenosis seen in single Tnf^tm2Gkl heterozygotes, including a decrease of the leaflets surface area and reduction of fibrosis

skeleton

joint inflammation ( J:264147 )

• mice show reduced clinical features of arthritis compared to single Tnf^tm2Gkl heterozygotes, with a reduction of pannus formation and cartilage/bone destruction

cellular

abnormal cell physiology ( J:264147 )

• valvular interstitial cells fail to become activated

• however, cultured valvular interstitial cells appear similar to wild-type cells and exhibit normal proliferation

abnormal cell adhesion ( J:264147 )

• synovial fibroblast and valvular interstitial cell adhesion to a fibronectin substrate is reduced by almost 50% compared to the levels in single Tnf^tm2Gkl heterozygotes but is somewhat higher than in wild-type cells

abnormal fibroblast physiology ( J:264147 )

• synovial fibroblasts fail to become activated

• however, cultured synovial fibroblasts appear similar to wild-type cells and exhibit normal proliferation

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:264147 )

• circulating TNF levels are elevated

abnormal wound healing ( J:264147 )

• synovial fibroblasts and valvular interstitial cells show only 40-45% closure of a wound in culture compared to 70-80% closure in single Tnf^tm2Gkl heterozygotes and about 20% in wild-type cells

immune system

increased circulating tumor necrosis factor level ( J:264147 )

• circulating TNF levels are elevated

increased tumor necrosis factor secretion ( J:264147 )

• levels of secreted TNF-alpha in supernatants of cultured synovial fibroblasts and valvular interstitial cells are elevated

joint inflammation ( J:264147 )

• mice show reduced clinical features of arthritis compared to single Tnf^tm2Gkl heterozygotes, with a reduction of pannus formation and cartilage/bone destruction

Genotype
MGI:6195560

cn2

• Allelic Composition: Tnfrsf1b^tm1.1Gkl/Tnfrsf1b^tm1.1Gkl; Tg(Col6a1-cre)1Gkl/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA

normal phenotype

no abnormal phenotype detected ( J:264147 )

• mice are born at the expected ratios, are viable, and fertile and do not display any spontaneous phenotypes