Phenotypes associated with this allele

• Allele Symbol: Adam17^tm1.1Srj
• Allele Name: targeted mutation 1.1, Stefan Rose-John
• Allele ID: MGI:4822480
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Adam17^tm1.1Srj/Adam17^tm1.1Srj	involves: 129S/SvEv	MGI:4839229
hm2	Adam17^tm1.1Srj/Adam17^tm1.1Srj	involves: 129S/SvEv * C57BL/6 * SJL	MGI:4822555
cn3	Adam10^tm1Beni/Adam10^tm1Beni Adam17^tm1.1Srj/Adam17^tm1.1Srj Tg(Pf4-icre)Q3Rsko/0	involves: 129/Sv * 129S/SvEv * C57BL/6	MGI:4839228

Genotype
MGI:4839229

hm1

• Allelic Composition: Adam17^tm1.1Srj/Adam17^tm1.1Srj
• Genetic Background: involves: 129S/SvEv

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

hematopoietic system

abnormal platelet physiology ( J:165863 )

• platelets fail to shed GPIbalpha unlike wild-type cells

• CCCP-treated platelets fail to cleave GPVI unlike similarly treated wild-type cells

• however, antibody-induced GPVI ectodomain shedding in vivo is normal

homeostasis/metabolism

abnormal platelet physiology ( J:165863 )

• platelets fail to shed GPIbalpha unlike wild-type cells

• CCCP-treated platelets fail to cleave GPVI unlike similarly treated wild-type cells

• however, antibody-induced GPVI ectodomain shedding in vivo is normal

Genotype
MGI:4822555

hm2

• Allelic Composition: Adam17^tm1.1Srj/Adam17^tm1.1Srj
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:163380 )

• in DSS-treated mice

postnatal lethality, incomplete penetrance ( J:163380 )

• fewer than expected mice are produced

digestive/alimentary system

digestive/alimentary phenotype ( J:163380 )

N • untreated mice exhibit regular colon mucosa arrangement and proliferation of colon tissue

abnormal enterocyte proliferation ( J:163380 )

• DSS-treated mice exhibit decreased proliferating nuclei in the intestinal crypts compared with similarly treated wild-type mice

• following treatment with TGFalpha, intestinal epithelial cell proliferation is increased compared to in similarly treated wild-type mice

increased susceptibility to induced colitis ( J:163380 )

• DSS-treated mice exhibit severe weight loss, increased mortality, severe colitis, loss of intestinal crypt structure, ulcerations of the colon, decreased proliferating nuclei in the intestinal crypts, increased intestinal barrier permeability, increased neutrophil activation, and elevated chemokine (KC and MCP-1), IL10, and IL11 levels in the colon organ cultures compared with similarly treated wild-type mice

• T cells confer susceptibility to induced colitis to recipient rag null mice

• however, treatment with TGFalpha reduces severity of weight loss

cardiovascular system

abnormal mitral valve cusp morphology ( J:163380 )

• mitral cusps are short compared with the ventricular volume unlike in wild-type mice

increased heart left ventricle size ( J:163380 )

• massive

vision/eye

eyelids open at birth ( J:163380 )

• eyelids are open at E17 unlike in wild-type mice

eye opacity ( J:163380 )

• in adult mice

immune system

increased susceptibility to induced colitis ( J:163380 )

• DSS-treated mice exhibit severe weight loss, increased mortality, severe colitis, loss of intestinal crypt structure, ulcerations of the colon, decreased proliferating nuclei in the intestinal crypts, increased intestinal barrier permeability, increased neutrophil activation, and elevated chemokine (KC and MCP-1), IL10, and IL11 levels in the colon organ cultures compared with similarly treated wild-type mice

• T cells confer susceptibility to induced colitis to recipient rag null mice

• however, treatment with TGFalpha reduces severity of weight loss

abnormal chemokine level ( J:163380 )

• colon organ cultures of DSS-treated mice exhibit elevated chemokine (KC and MCP-1) compared with cultures from similarly treated wild-type mice

abnormal interleukin secretion ( J:163380 )

• the colon organ cultures of DSS-treated mice exhibit increased IL1- and IL11 compared with cultures from similarly treated wild-type mice

increased interleukin-10 secretion ( J:163380 )

• in the colon organ cultures of DSS-treated mice

skin inflammation ( J:163380 )

• mice exhibit secondary skin inflammation and (peri)follicular mixed inflammatory infiltrate unlike wild-type mice

growth/size/body

increased susceptibility to weight loss ( J:163380 )

• severe in DSS-treated mice

• however, treatment with TGFalpha reduces severity of weight loss

homeostasis/metabolism

abnormal chemokine level ( J:163380 )

• colon organ cultures of DSS-treated mice exhibit elevated chemokine (KC and MCP-1) compared with cultures from similarly treated wild-type mice

endocrine/exocrine glands

abnormal mammary gland duct morphology ( J:163380 )

♀ • milk duct development is reduced compared to in wild-type mice

integument

abnormal mammary gland duct morphology ( J:163380 )

♀ • milk duct development is reduced compared to in wild-type mice

skin inflammation ( J:163380 )

• mice exhibit secondary skin inflammation and (peri)follicular mixed inflammatory infiltrate unlike wild-type mice

distorted hair follicle pattern ( J:163380 )

• wave hair follicles exhibit a partly disorganized arrangement compared to in wild-type mice

cellular

abnormal enterocyte proliferation ( J:163380 )

• DSS-treated mice exhibit decreased proliferating nuclei in the intestinal crypts compared with similarly treated wild-type mice

• following treatment with TGFalpha, intestinal epithelial cell proliferation is increased compared to in similarly treated wild-type mice

Genotype
MGI:4839228

cn3

• Allelic Composition: Adam10^tm1Beni/Adam10^tm1Beni; Adam17^tm1.1Srj/Adam17^tm1.1Srj; Tg(Pf4-icre)Q3Rsko/0
• Genetic Background: involves: 129/Sv * 129S/SvEv * C57BL/6

mortality/aging

preweaning lethality, incomplete penetrance ( J:165863 )

• adult mice deficient in both metalloproteinases were rarely obtained (frequency: 2.5%)

hematopoietic system

abnormal platelet physiology ( J:165863 )

• when bone marrow is transplanted into irradiated wild-type mice, platelets treated with a calmodulin inhibitor (W7) or a mitochondrial damage reagent (CCCP) fail to shed GPVI in vitro unlike similarly treated wild-type cells

• however, in vivo shedding is normal

homeostasis/metabolism

abnormal platelet physiology ( J:165863 )

• when bone marrow is transplanted into irradiated wild-type mice, platelets treated with a calmodulin inhibitor (W7) or a mitochondrial damage reagent (CCCP) fail to shed GPVI in vitro unlike similarly treated wild-type cells

• however, in vivo shedding is normal