Strain Name:

B6.129X1-Mmp8tm1Otin/J

Stock Number:

005514

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129X1-Mmp8tm1Lotn/J    (Changed: 10-SEP-14 )
B6;129X1-Mmp8tm1Lotn/J    (Changed: 27-SEP-10 )
Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation?+N1p (15-JAN-06)
Generation Definitions
 
Donating Investigator Steven D Shapiro,   University of Pittsburgh

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of peripheral blood cells. Male mice homozygous for the mutation are more susceptible to experimentally induced invasive papillomas and fibrosarcomas. Latency of papilloma tumor formation is shorter. Female homozygotes exhibit increased skin cancer incidence when treated with tamoxifen or ovarectomy. Carcinogen administration causes persistent inflammatory response with neutrophil accumulation at the site of injection. Lipopolysaccharide (LPS) challenge causes a two-fold increase in polymorphonuclear cell accumulation in affected lung tissue of male homozygotes. This mutant mouse strain may be useful in studies of carcinogenesis, metastasis, and inflammation.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 2 to 4. The construct was electroporated into 129X1/SvJ-derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6 for 10 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mmp8
022092   B6N(Cg)-Mmp8tm1.1(KOMP)Vlcg/J
View Strains carrying other alleles of Mmp8     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Mmp8tm1Otin/Mmp8tm1Otin

        involves: 129X1/SvJ * C57BL/6J
  • tumorigenesis
  • increased tumor incidence
    • succeptibility to tumor induction significantly greater in males than in females and latency is shorter   (MGI Ref ID J:86393)
    • ovarectomy or tamoxifen treatment increased skin cancer incidence in females   (MGI Ref ID J:86393)
    • rate of progression from benign to malignant was normal   (MGI Ref ID J:86393)
    • increased fibrosarcoma incidence
      • formed in response to intradermal injection of methylcholanthrene   (MGI Ref ID J:86393)
      • all were invasive tumors   (MGI Ref ID J:86393)
    • increased papilloma incidence
      • formed in response to DMBA+TPA   (MGI Ref ID J:86393)
  • immune system phenotype
  • abnormal inflammatory response
    • inflammatory response slower to establish itself   (MGI Ref ID J:86393)
    • chronic inflammation
      • sustained inflammatory response to injected carcinogens develops   (MGI Ref ID J:86393)
      • accumulated cells were neutrophils   (MGI Ref ID J:86393)
  • increased susceptibility to bacterial infection
    • intratracheal lipopolysaccharide (LPS) treatment results in 2 fold increase in polymorphonuclear cell accumulation in the alveolar space and approximately 3 fold increase in myeloperoxidase activity in bronchioalveolar lavage lysate   (MGI Ref ID J:97118)

Mmp8tm1Otin/Mmp8tm1Otin

        involves: 129X1/SvJ * C57BL/6
  • immune system phenotype
  • *normal* immune system phenotype
    • mice exhibit a normal local Shwartman response namely thrombohemorrhagic vasculitis   (MGI Ref ID J:113463)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Mmp8tm1Otin/Mmp8tm1Otin

        involves: 129X1/SvJ
  • immune system phenotype
  • *normal* immune system phenotype
    • mice exhibit normal response to Coxsackievirus B3 (CVB3) infection   (MGI Ref ID J:148442)
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Skin Cancers
      Skin Cancers: Induced

Cell Biology Research
Defects in Extracellular Matrix Molecules

Immunology, Inflammation and Autoimmunity Research
Inflammation
      Neutrophil defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mmp8tm1Otin
Allele Name targeted mutation 1, Carlos Lopez-Otin
Allele Type Targeted (Null/Knockout)
Common Name(s) MMP-8 KO; Mmp8-; Mmp8tm1Lotn; collagenase-2 deficient;
Mutation Made By Jennifer Cusick,   University of Pittsburgh
Strain of Origin129X1/SvJ
ES Cell Line NameRW-4
ES Cell Line Strain129X1/SvJ
Gene Symbol and Name Mmp8, matrix metallopeptidase 8
Chromosome 9
Gene Common Name(s) BB138268; CLG1; Collagenase-2; HNC; MMP-8; PMNL-CL; expressed sequence BB138268;
Molecular Note Part of exon 2 and all of exons 3 and 4 were replaced with a PGK-neomycin gene. Lack of protein product verified by immunofluorescence analysis blood neutrophils and by Western blot analysis. [MGI Ref ID J:86393]

Genotyping

Genotyping Information

Genotyping Protocols

Mmp8tm1Lotn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Balbin M; Fueyo A; Tester AM; Pendas AM; Pitiot AS; Astudillo A; Overall CM; Shapiro SD; Lopez-Otin C. 2003. Loss of collagenase-2 confers increased skin tumor susceptibility to male mice. Nat Genet 35(3):252-7. [PubMed: 14517555]  [MGI Ref ID J:86393]

Additional References

Mmp8tm1Otin related

Albaiceta GM; Gutierrez-Fernandez A; Garcia-Prieto E; Puente XS; Parra D; Astudillo A; Campestre C; Cabrera S; Gonzalez-Lopez A; Fueyo A; Taboada F; Lopez-Otin C. 2010. Absence or inhibition of matrix metalloproteinase-8 decreases ventilator-induced lung injury. Am J Respir Cell Mol Biol 43(5):555-63. [PubMed: 19995943]  [MGI Ref ID J:177811]

Cheung C; Marchant D; Walker EK; Luo Z; Zhang J; Yanagawa B; Rahmani M; Cox J; Overall C; Senior RM; Luo H; McManus BM. 2008. Ablation of matrix metalloproteinase-9 increases severity of viral myocarditis in mice. Circulation 117(12):1574-82. [PubMed: 18332263]  [MGI Ref ID J:148442]

Craig VJ; Quintero PA; Fyfe SE; Patel AS; Knolle MD; Kobzik L; Owen CA. 2013. Profibrotic Activities for Matrix Metalloproteinase-8 during Bleomycin-Mediated Lung Injury. J Immunol 190(8):4283-96. [PubMed: 23487425]  [MGI Ref ID J:195119]

Dolinay T; Wu W; Kaminski N; Ifedigbo E; Kaynar AM; Szilasi M; Watkins SC; Ryter SW; Hoetzel A; Choi AM. 2008. Mitogen-activated protein kinases regulate susceptibility to ventilator-induced lung injury. PLoS ONE 3(2):e1601. [PubMed: 18270588]  [MGI Ref ID J:132187]

Fang C; Wen G; Zhang L; Lin L; Moore A; Wu S; Ye S; Xiao Q. 2013. An important role of matrix metalloproteinase-8 in angiogenesis in vitro and in vivo. Cardiovasc Res 99(1):146-55. [PubMed: 23512982]  [MGI Ref ID J:211445]

Folgueras AR; Fueyo A; Garcia-Suarez O; Cox J; Astudillo A; Tortorella P; Campestre C; Gutierrez-Fernandez A; Fanjul-Fernandez M; Pennington CJ; Edwards DR; Overall CM; Lopez-Otin C. 2008. Collagenase-2 deficiency or inhibition impairs experimental autoimmune encephalomyelitis in mice. J Biol Chem 283(14):9465-74. [PubMed: 18245084]  [MGI Ref ID J:135284]

Garcia-Prieto E; Gonzalez-Lopez A; Cabrera S; Astudillo A; Gutierrez-Fernandez A; Fanjul-Fernandez M; Batalla-Solis E; Puente XS; Fueyo A; Lopez-Otin C; Albaiceta GM. 2010. Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10. PLoS One 5(10):e13242. [PubMed: 20949050]  [MGI Ref ID J:166060]

Gonzalez-Lopez A; Aguirre A; Lopez-Alonso I; Amado L; Astudillo A; Fernandez-Garcia MS; Suarez MF; Batalla-Solis E; Colado E; Albaiceta GM. 2012. MMP-8 deficiency increases TLR/RAGE ligands S100A8 and S100A9 and exacerbates lung inflammation during endotoxemia. PLoS One 7(6):e39940. [PubMed: 22768176]  [MGI Ref ID J:187906]

Grant Rowe R; Keena D; Sabeh F; Willis AL; Weiss SJ. 2011. Pulmonary fibroblasts mobilize the membrane-tethered matrix metalloprotease, MT1-MMP, to destructively remodel and invade interstitial type I collagen barriers. Am J Physiol Lung Cell Mol Physiol 301(5):L683-92. [PubMed: 21840960]  [MGI Ref ID J:178018]

Gueders MM; Balbin M; Rocks N; Foidart JM; Gosset P; Louis R; Shapiro S; Lopez-Otin C; Noel A; Cataldo DD. 2005. Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J Immunol 175(4):2589-97. [PubMed: 16081833]  [MGI Ref ID J:107491]

Gutierrez-Fernandez A; Fueyo A; Folgueras AR; Garabaya C; Pennington CJ; Pilgrim S; Edwards DR; Holliday DL; Jones JL; Span PN; Sweep FC; Puente XS; Lopez-Otin C. 2008. Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion. Cancer Res 68(8):2755-63. [PubMed: 18413742]  [MGI Ref ID J:133961]

Gutierrez-Fernandez A; Inada M; Balbin M; Fueyo A; Pitiot AS; Astudillo A; Hirose K; Hirata M; Shapiro SD; Noel A; Werb Z; Krane SM; Lopez-Otin C; Puente XS. 2007. Increased inflammation delays wound healing in mice deficient in collagenase-2 (MMP-8). FASEB J 21(10):2580-91. [PubMed: 17392479]  [MGI Ref ID J:134846]

Hirahashi J; Mekala D; Van Ziffle J; Xiao L; Saffaripour S; Wagner DD; Shapiro SD; Lowell C; Mayadas TN. 2006. Mac-1 signaling via Src-family and Syk kinases results in elastase-dependent thrombohemorrhagic vasculopathy. Immunity 25(2):271-83. [PubMed: 16872848]  [MGI Ref ID J:113463]

Khatwa UA; Kleibrink BE; Shapiro SD; Subramaniam M. 2010. MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis. J Leukoc Biol 87(1):69-77. [PubMed: 19801498]  [MGI Ref ID J:155984]

Koenig GC; Rowe RG; Day SM; Sabeh F; Atkinson JJ; Cooke KR; Weiss SJ. 2012. MT1-MMP-Dependent Remodeling of Cardiac Extracellular Matrix Structure and Function Following Myocardial Infarction. Am J Pathol 180(5):1863-78. [PubMed: 22464947]  [MGI Ref ID J:183626]

Korpi JT; Kervinen V; Maklin H; Vaananen A; Lahtinen M; Laara E; Ristimaki A; Thomas G; Ylipalosaari M; Astrom P; Lopez-Otin C; Sorsa T; Kantola S; Pirila E; Salo T. 2008. Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer. Br J Cancer 98(4):766-75. [PubMed: 18253113]  [MGI Ref ID J:134226]

Kuula H; Salo T; Pirila E; Tuomainen AM; Jauhiainen M; Uitto VJ; Tjaderhane L; Pussinen PJ; Sorsa T. 2009. Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis. Infect Immun 77(2):850-9. [PubMed: 19029300]  [MGI Ref ID J:143755]

Laxton RC; Hu Y; Duchene J; Zhang F; Zhang Z; Leung KY; Xiao Q; Scotland RS; Hodgkinson CP; Smith K; Willeit J; Lopez-Otin C; Simpson IA; Kiechl S; Ahluwalia A; Xu Q; Ye S. 2009. A role of matrix metalloproteinase-8 in atherosclerosis. Circ Res 105(9):921-9. [PubMed: 19745165]  [MGI Ref ID J:169956]

Lin M; Jackson P; Tester AM; Diaconu E; Overall CM; Blalock JE; Pearlman E. 2008. Matrix metalloproteinase-8 facilitates neutrophil migration through the corneal stromal matrix by collagen degradation and production of the chemotactic peptide Pro-Gly-Pro. Am J Pathol 173(1):144-53. [PubMed: 18556780]  [MGI Ref ID J:137367]

Owen CA; Hu Z; Lopez-Otin C; Shapiro SD. 2004. Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase. J Immunol 172(12):7791-803. [PubMed: 15187163]  [MGI Ref ID J:97118]

Quintero PA; Knolle MD; Cala LF; Zhuang Y; Owen CA. 2010. Matrix metalloproteinase-8 inactivates macrophage inflammatory protein-1 alpha to reduce acute lung inflammation and injury in mice. J Immunol 184(3):1575-88. [PubMed: 20042585]  [MGI Ref ID J:159502]

Sabeh F; Li XY; Saunders TL; Rowe RG; Weiss SJ. 2009. Secreted versus membrane-anchored collagenases: relative roles in fibroblast-dependent collagenolysis and invasion. J Biol Chem 284(34):23001-11. [PubMed: 19542530]  [MGI Ref ID J:153449]

Sounni NE; Dehne K; van Kempen L; Egeblad M; Affara NI; Cuevas I; Wiesen J; Junankar S; Korets L; Lee J; Shen J; Morrison CJ; Overall CM; Krane SM; Werb Z; Boudreau N; Coussens LM. 2010. Stromal regulation of vessel stability by MMP14 and TGF{beta}. Dis Model Mech 3(5-6):317-32. [PubMed: 20223936]  [MGI Ref ID J:159238]

Van Lint P; Wielockx B; Puimege L; Noel A; Lopez-Otin C; Libert C. 2005. Resistance of collagenase-2 (matrix metalloproteinase-8)-deficient mice to TNF-induced lethal hepatitis. J Immunol 175(11):7642-9. [PubMed: 16301674]  [MGI Ref ID J:122165]

Vandenbroucke RE; Dejonckheere E; Van Lint P; Demeestere D; Van Wonterghem E; Vanlaere I; Puimege L; Van Hauwermeiren F; De Rycke R; Mc Guire C; Campestre C; Lopez-Otin C; Matthys P; Leclercq G; Libert C. 2012. Matrix Metalloprotease 8-Dependent Extracellular Matrix Cleavage at the Blood-CSF Barrier Contributes to Lethality during Systemic Inflammatory Diseases. J Neurosci 32(29):9805-9816. [PubMed: 22815495]  [MGI Ref ID J:186468]

Xiao Q; Zhang F; Lin L; Fang C; Wen G; Tsai TN; Pu X; Sims D; Zhang Z; Yin X; Thomaszewski B; Schmidt B; Mayr M; Suzuki K; Xu Q; Ye S. 2013. Functional role of matrix metalloproteinase-8 in stem/progenitor cell migration and their recruitment into atherosclerotic lesions. Circ Res 112(1):35-47. [PubMed: 23071158]  [MGI Ref ID J:212875]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryopreserved Embryos
    Available to most shipping destinations1
    This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.

    1 Shipments cannot be made to Australia due to Australian government import restrictions.
    2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.
  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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