Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote         (Female x Male)   02-NOV-10 Species laboratory mouse Generation F?+4 (29-JUN-11) Generation Definitions   Donating Investigator Carl P Blobel,   Hospital for Special Surgery-Weill Med

Description
Mice homozygous for this Tace^flox allele are viable and fertile, with loxP sites flanking exon 2 of the targeted gene. When bred to mice that express Cre recombinase, the resulting offspring will have the floxed sequences deleted in the cre-expressing tissue producing a null allele. As the proinflammatory cytokine TNF-α and other other cell receptors are synthesized as membrane-bound precursors that need to be proteolytically released by functional TNF-α converting enzyme (TACE or Adam17 [a disintegrin and metallopeptidase domain 17]), these Tace^flox mutant mice may be useful in generating conditional mutations for studying TNF-sheddase function, TNF-related autoimmune diseases.

Development
A targeting vector was designed to insert a loxP site and frt-flanked PGK-neo cassette upstream of exon 2, and a second loxP site downstream of exon 2 of the targeted gene. The donating investigator reports that the construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6 females to establish the colony. The mutant mice (C57BL/6;129P2/OlaHsd genetic background) were then bred to mice expressing Flp recombinase (B6;SJL genetic background; see Stock No. 003800) to remove the frt-flanked neo cassette. The resulting Tace^flox mice (with loxP site and single frt site remaining upstream of exon 2, and a second loxP site downstream of exon 2) were maintained on this mixed genetic background for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

	Control
	100492 B6129PF1/J	(approximate)
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Inflammatory Skin and Bowel Disease, Neonatal; NISBD   (ADAM17)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Adam17^tm1.2Bbl/Adam17^tm1.2Bbl

        involves: 129P2/OlaHsd * C57BL/6

• normal phenotype
• no abnormal phenotype detected
  • mice are viable and fertile   (MGI Ref ID J:139846)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Cancer Research
Growth Factors/Receptors/Cytokines

Cell Biology Research
Protein Processing

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines

Research Tools
Cancer Research
Cre-lox System
      loxP-flanked Sequences
Developmental Biology Research
      Cre-lox System
Immunology and Inflammation Research
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Adam17tm1.2Bbl
Allele Name		targeted mutation 1.2, Carl P Blobel
Allele Type		Targeted (Floxed/Frt)
Mutation Made By		Carl Blobel,   Hospital for Special Surgery-Weill Med
Strain of Origin		129P2/OlaHsd
Gene Symbol and Name		Adam17, a disintegrin and metallopeptidase domain 17
Chromosome		12
Gene Common Name(s)		ADAM18; CD156B; CSVP; NISBD; TACE; Tace; tumor necrosis factor-alpha converting enzyme;
Molecular Note		A targeting vector was designed to insert a loxP site and frt-flanked PGK-neo cassette upstream of exon 2, and a second loxP site downstream of exon 2 of the targeted gene. The resulting mutant mice were then bred to mice expressing Flp recombinase to remove the frt-flanked neo cassette. [MGI Ref ID J:139846]

Genotyping

Genotyping Information

Genotyping Protocols

Adam17^tm1.2Bblalternate1, Standard PCR
Adam17^tm1.2Bbl, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Horiuchi K; Kimura T; Miyamoto T; Miyamoto K; Akiyama H; Takaishi H; Morioka H; Nakamura T; Okada Y; Blobel CP; Toyama Y. 2009. Conditional inactivation of TACE by a Sox9 promoter leads to osteoporosis and increased granulopoiesis via dysregulation of IL-17 and G-CSF. J Immunol 182(4):2093-101. [PubMed: 19201862]  [MGI Ref ID J:144795]

Horiuchi K; Kimura T; Miyamoto T; Takaishi H; Okada Y; Toyama Y; Blobel CP. 2007. Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. J Immunol 179(5):2686-9. [PubMed: 17709479]  [MGI Ref ID J:139846]

Additional References

Adam17^tm1.2Bbl related

La Marca R; Cerri F; Horiuchi K; Bachi A; Feltri ML; Wrabetz L; Blobel CP; Quattrini A; Salzer JL; Taveggia C. 2011. TACE (ADAM17) inhibits Schwann cell myelination. Nat Neurosci 14(7):857-65. [PubMed: 21666671]  [MGI Ref ID J:174007]

Long C; Wang Y; Herrera AH; Horiuchi K; Walcheck B. 2010. In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E. coli-mediated peritonitis. J Leukoc Biol 87(6):1097-101. [PubMed: 20154226]  [MGI Ref ID J:162272]

Murthy A; Defamie V; Smookler DS; Di Grappa MA; Horiuchi K; Federici M; Sibilia M; Blobel CP; Khokha R. 2010. Ectodomain shedding of EGFR ligands and TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis in mice. J Clin Invest 120(8):2731-44. [PubMed: 20628198]  [MGI Ref ID J:163773]

Xu H; Zhu J; Smith S; Foldi J; Zhao B; Chung AY; Outtz H; Kitajewski J; Shi C; Weber S; Saftig P; Li Y; Ozato K; Blobel CP; Ivashkiv LB; Hu X. 2012. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nat Immunol 13(7):642-50. [PubMed: 22610140]  [MGI Ref ID J:187656]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Homozygote x Homozygote         (Female x Male)   02-NOV-10
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	100492 B6129PF1/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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