Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   21-SEP-12 Species laboratory mouse Generation N7pN1+ (25-MAY-12) Generation Definitions   Donating Investigator Richard L. Gallo,   University of California at San Diego

Description
The mouse Camp gene is an ortholog of the human gene CAMP, which encodes the precursor of cathelicidin antimicrobial peptide LL-37 (or CRAMP in mouse). Expressed mucosal epithelial cells, circulating neutrophils, and myeloid bone marrow cells, Camp is an essential part of the first line of defense against infection. In addition to antimicrobial activity, cathelicidin antimicrobial peptide plays a role in NK cell-mediated tumor growth suppression, and when secreted by neutrophils acts, as an attractant for monocytes, promoting wound healing or angiogenesis. Mouse CRAMP is implicated in adaptive immune response regulation and can interfere with TLR function via interactions with hyaluronan. Mice deficient in CRAMP are more susceptible to experimentally induced necrotic skin infection with Group A Streptococcus, urinary tract infection with uropathogenic E. coli, Pseudomonas aeruginosa infection, and meningococcal Neisseria meningitidis infection. Skin lesions, due to Group A Streptococcus infection, are larger and persist longer in homozygotes when compared to controls. Heterozygotes exhibit an intermediate Group A Streptococcus bacterial susceptibility phenotype. Within 1 hour of infection, more uropathogenic E. coli bacteria are attached to urinary bladder mucosa of mutant mice. 48 hours after infection, the number of bacteria in the urinary tract of homozygous mice is higher than wildtype controls. Mutant mice challenged with uropathogenic E. coli developed more severe urinary tract infections and exhibit higher mortality from septicemia when compared to controls. After intranasal Pseudomonas aeruginosa inoculation, CRAMP deficient mice exhibit significantly higher levels of bacterial CFUs compared to controls. When pretreated with flagellin, only one third of infected CRAMP deficient mice survived, compared to complete survival of all infected wildtype mice. Homozygotes also develop more severe infection of Pseudomonas aeruginosa in induced corneal keratitis. An increased invasion rate is observed after oral administration of Listeria monocytogenes to homozygotes. In an experimentally induced skin inflammation model for atopic dermatitis, homozygotes exhibit enhanced swelling and more severe epidermal hypertrophy. The epidermal permeability barrier is functionally impaired in homozygotes. Induced irritation of the skin of homozygous mice by stratum corneum tryptic enzyme or physical abrastion results in reduced inflammatory infiltrate, when compared to controls. In vaccinia virus skin infection (eczema vaccinatum), homozygotes on the BALB/c background have higher levels of virus replication in skin biopsies compared to controls. Knock out mice are more susceptible to meningococcal Neisseria meningitidis infection with higher CFU load and mortality rate. When B and T cells from homozygotes are cultured in Th2-inducing conditions, the mutant B cells produce less IgG1 and IgE, and a higher ratio of mutant IL-4+ T cells is observed, when compared to cultures isolated from wildtype mice. Xenograft tumors growth is accelerated in homozygotes: B16.F10 melanoma tumors grow faster and obtain a larger size, and RMA-S lymphoma cell tumor development is earlier when compared to controls. NK cells isolated from homozygotes display defective cytotoxic activity. 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 (mRNA or protein) is detected by Northern blot analysis of bone marrow or by Western blot analysis of epidermis from homozygotes.

Development
A targeting vector containing a PGK-neo cassette was used to disrupt exons 3 and 4. The construct was electroporated into unspecified 129X1/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to 129/SvJ female mice, and then backcrossed to C57BL/6J for seven generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

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.

Camp^tm1Rlg/Camp⁺

        involves: 129X1/SvJ * C57BL/6

• immune system phenotype
• increased susceptibility to bacterial infection
  • heterozygotes are more susceptible to Group A Streptococcus infection, developing intermediate sized lesions   (MGI Ref ID J:72924)

Camp^tm1Rlg/Camp^tm1Rlg

        involves: 129X1/SvJ * C57BL/6

• immune system phenotype
• increased susceptibility to bacterial infection
  • homozygotes are more susceptible to Group A Streptococcus infection, developing larger areas of infection and showing a more rapid increase in lesion areas and longer persistence of lesions   (MGI Ref ID J:72924)

Camp^tm1Rlg/Camp^tm1Rlg

        129X1/SvJ-Camp^tm1Rlg

• mortality/aging
• increased susceptibility to bacterial infection induced morbidity/mortality
  • homozygotes with urinary tract infection (caused by E.coli infection) show increased mortality, with 3 of 18 dying from septicemia compared to none of wild-type   (MGI Ref ID J:109553)
• immune system phenotype
• increased susceptibility to bacterial infection
  • increased susceptibility to uropathogenic E. coli infection; exhibit a higher infection rate (increased presence of bacteria in urinary tract) and higher numbers of bacteria attached to bladders and surviving on epithelial cells after 30 min   (MGI Ref ID J:109553)
  • homozygotes with urinary tract infection exhibit higher number of bacteria in kidneys and larger size of kidneys and have more severe systemic signs of infection such as weight loss and increased mortality   (MGI Ref ID J:109553)
• • increased susceptibility to bacterial infection induced morbidity/mortality
    • homozygotes with urinary tract infection (caused by E.coli infection) show increased mortality, with 3 of 18 dying from septicemia compared to none of wild-type   (MGI Ref ID J:109553)

View Research Applications

Research Applications

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

Cancer Research
Genes Regulating Growth and Proliferation

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency

Internal/Organ Research
Wound Healing

Research Tools
Cancer Research
      B, T, and NK cell deficiency, xenograft/transplant host
      tumor immunology
Immunology and Inflammation Research
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Camptm1Rlg
Allele Name		targeted mutation 1, Richard L Gallo
Allele Type		Targeted (knock-out)
Common Name(s)		Camp-; Cnlp-; Cnlp-null; Cramp-ko;
Mutation Made By		Carlos Aguilera,   University of California at San Diego
Strain of Origin		129X1/SvJ
Gene Symbol and Name		Camp, cathelicidin antimicrobial peptide
Chromosome		9
Gene Common Name(s)		CAP-18; CAP18; CRAMP; Cnlp; Cramp; FALL-39; FALL39; LL37; MCLP; cathelin related antimicrobial peptide; cathelin-like protein;
Molecular Note		Exons 3 and 4, which encode the entire mature domain of the protein, were replaced with a PGK-neo cassette via homologous recombination. Northern blot analysis using a probe to exon 4 confirmed the absence of gene expression in bone marrow of homozygous mutant animals. [MGI Ref ID J:72924]

Genotyping

Genotyping Information

Genotyping Protocols

Camp^tm1Rlg,

Separated MCA

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Nizet V; Ohtake T; Lauth X; Trowbridge J; Rudisill J; Dorschner RA; Pestonjamasp V; Piraino J; Huttner K; Gallo RL. 2001. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature 414(6862):454-7. [PubMed: 11719807]  [MGI Ref ID J:72924]

Additional References

Camp^tm1Rlg related

Aberg KM; Man MQ; Gallo RL; Ganz T; Crumrine D; Brown BE; Choi EH; Kim DK; Schroder JM; Feingold KR; Elias PM. 2008. Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers. J Invest Dermatol 128(4):917-25. [PubMed: 17943185]  [MGI Ref ID J:135506]

Bergman P; Johansson L; Wan H; Jones A; Gallo RL; Gudmundsson GH; Hokfelt T; Jonsson AB; Agerberth B. 2006. Induction of the antimicrobial peptide CRAMP in the blood-brain barrier and meninges after meningococcal infection. Infect Immun 74(12):6982-91. [PubMed: 17030578]  [MGI Ref ID J:116071]

Braff MH; Zaiou M; Fierer J; Nizet V; Gallo RL. 2005. Keratinocyte production of cathelicidin provides direct activity against bacterial skin pathogens. Infect Immun 73(10):6771-81. [PubMed: 16177355]  [MGI Ref ID J:104215]

Buchau AS; Morizane S; Trowbridge J; Schauber J; Kotol P; Bui JD; Gallo RL. 2010. The host defense peptide cathelicidin is required for NK cell-mediated suppression of tumor growth. J Immunol 184(1):369-78. [PubMed: 19949065]  [MGI Ref ID J:159045]

Chromek M; Arvidsson I; Karpman D. 2012. The antimicrobial peptide cathelicidin protects mice from Escherichia coli O157:H7-mediated disease. PLoS One 7(10):e46476. [PubMed: 23077510]  [MGI Ref ID J:192217]

Chromek M; Slamova Z; Bergman P; Kovacs L; Podracka L; Ehren I; Hokfelt T; Gudmundsson GH; Gallo RL; Agerberth B; Brauner A. 2006. The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 12(6):636-41. [PubMed: 16751768]  [MGI Ref ID J:109553]

Di Nardo A; Yamasaki K; Dorschner RA; Lai Y; Gallo RL. 2008. Mast cell cathelicidin antimicrobial peptide prevents invasive group a streptococcus infection of the skin. J Immunol 180(11):7565-73. [PubMed: 18490758]  [MGI Ref ID J:136326]

Gregorio J; Meller S; Conrad C; Di Nardo A; Homey B; Lauerma A; Arai N; Gallo RL; Digiovanni J; Gilliet M. 2010. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J Exp Med 207(13):2921-30. [PubMed: 21115688]  [MGI Ref ID J:176867]

Howell MD; Gallo RL; Boguniewicz M; Jones JF; Wong C; Streib JE; Leung DY. 2006. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 24(3):341-8. [PubMed: 16546102]  [MGI Ref ID J:113325]

Howell MD; Jones JF; Kisich KO; Streib JE; Gallo RL; Leung DY. 2004. Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum. J Immunol 172(3):1763-7. [PubMed: 14734759]  [MGI Ref ID J:87659]

Huang LC; Reins RY; Gallo RL; McDermott AM. 2007. Cathelicidin-deficient (Cnlp -/- ) mice show increased susceptibility to Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 48(10):4498-508. [PubMed: 17898271]  [MGI Ref ID J:126930]

Iimura M; Gallo RL; Hase K; Miyamoto Y; Eckmann L; Kagnoff MF. 2005. Cathelicidin mediates innate intestinal defense against colonization with epithelial adherent bacterial pathogens. J Immunol 174(8):4901-7. [PubMed: 15814717]  [MGI Ref ID J:98169]

Jann NJ; Schmaler M; Kristian SA; Radek KA; Gallo RL; Nizet V; Peschel A; Landmann R. 2009. Neutrophil antimicrobial defense against Staphylococcus aureus is mediated by phagolysosomal but not extracellular trap-associated cathelicidin. J Leukoc Biol 86(5):1159-69. [PubMed: 19638500]  [MGI Ref ID J:155026]

Kin NW; Chen Y; Stefanov EK; Gallo RL; Kearney JF. 2011. Cathelin-related antimicrobial peptide differentially regulates T- and B-cell function. Eur J Immunol 41(10):3006-16. [PubMed: 21773974]  [MGI Ref ID J:177604]

Kovach MA; Ballinger MN; Newstead MW; Zeng X; Bhan U; Yu FS; Moore BB; Gallo RL; Standiford TJ. 2012. Cathelicidin-related antimicrobial peptide is required for effective lung mucosal immunity in Gram-negative bacterial pneumonia. J Immunol 189(1):304-11. [PubMed: 22634613]  [MGI Ref ID J:188955]

Matsushima H; Geng S; Lu R; Okamoto T; Yao Y; Mayuzumi N; Kotol PF; Chojnacki BJ; Miyazaki T; Gallo RL; Takashima A. 2013. Neutrophil differentiation into a unique hybrid population exhibiting dual phenotype and functionality of neutrophils and dendritic cells. Blood 121(10):1677-89. [PubMed: 23305731]  [MGI Ref ID J:195440]

Menard S; Forster V; Lotz M; Gutle D; Duerr CU; Gallo RL; Henriques-Normark B; Putsep K; Andersson M; Glocker EO; Hornef MW. 2008. Developmental switch of intestinal antimicrobial peptide expression. J Exp Med 205(1):183-93. [PubMed: 18180308]  [MGI Ref ID J:131123]

Morioka Y; Yamasaki K; Leung D; Gallo RL. 2008. Cathelicidin antimicrobial peptides inhibit hyaluronan-induced cytokine release and modulate chronic allergic dermatitis. J Immunol 181(6):3915-22. [PubMed: 18768846]  [MGI Ref ID J:139105]

Ren SX; Cheng AS; To KF; Tong JH; Li MS; Shen J; Wong CC; Zhang L; Chan RL; Wang XJ; Ng SS; Chiu LC; Marquez VE; Gallo RL; Chan FK; Yu J; Sung JJ; Wu WK; Cho CH. 2012. Host immune defense peptide LL-37 activates caspase-independent apoptosis and suppresses colon cancer. Cancer Res 72(24):6512-23. [PubMed: 23100468]  [MGI Ref ID J:193633]

Rosenberger CM; Gallo RL; Finlay BB. 2004. Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci U S A 101(8):2422-7. [PubMed: 14983025]  [MGI Ref ID J:88643]

Soehnlein O; Wantha S; Simsekyilmaz S; Doring Y; Megens RT; Mause SF; Drechsler M; Smeets R; Weinandy S; Schreiber F; Gries T; Jockenhoevel S; Moller M; Vijayan S; van Zandvoort MA; Agerberth B; Pham CT; Gallo RL; Hackeng TM; Liehn EA; Zernecke A; Klee D; Weber C. 2011. Neutrophil-derived cathelicidin protects from neointimal hyperplasia. Sci Transl Med 3(103):103ra98. [PubMed: 21974936]  [MGI Ref ID J:178318]

Strandberg KL; Richards SM; Tamayo R; Reeves LT; Gunn JS. 2012. An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice. PLoS One 7(11):e49588. [PubMed: 23166721]  [MGI Ref ID J:194792]

Wang Z; Lai Y; Bernard JJ; Macleod DT; Cogen AL; Moss B; Di Nardo A. 2012. Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides. J Immunol 188(1):345-57. [PubMed: 22140255]  [MGI Ref ID J:180895]

Wang Z; MacLeod DT; Di Nardo A. 2012. Commensal bacteria lipoteichoic acid increases skin mast cell antimicrobial activity against vaccinia viruses. J Immunol 189(4):1551-8. [PubMed: 22772452]  [MGI Ref ID J:189762]

Yamasaki K; Di Nardo A; Bardan A; Murakami M; Ohtake T; Coda A; Dorschner RA; Bonnart C; Descargues P; Hovnanian A; Morhenn VB; Gallo RL. 2007. Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nat Med 13(8):975-80. [PubMed: 17676051]  [MGI Ref ID J:125090]

Yu FS; Cornicelli MD; Kovach MA; Newstead MW; Zeng X; Kumar A; Gao N; Yoon SG; Gallo RL; Standiford TJ. 2010. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide. J Immunol 185(2):1142-9. [PubMed: 20566829]  [MGI Ref ID J:162021]

Zhang Z; Zhong W; Hinrichs D; Wu X; Weinberg A; Hall M; Spencer D; Wegmann K; Rosenbaum JT. 2010. Activation of OX40 augments Th17 cytokine expression and antigen-specific uveitis. Am J Pathol 177(6):2912-20. [PubMed: 20952591]  [MGI Ref ID J:170784]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   21-SEP-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
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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phone:	207-288-6470
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