Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10F?+G12N1F2 (06-DEC-07)   Donating Investigator Tanya Mayadas,   Brigham and Women's Hosp/Harvard Med Sch

Description
Mice that are homozygous for the Itgam^tm1Myd targeted mutation are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. No Itgam protein is detected in homozygous mutant neutrophils. Homozygous null animals have a diminished ability to clear thioglycollate-induced neutrophils, have reduced mast cell numbers in the dorsal skin and peritoneal wall/cavity, and are less susceptible to cerebral ischemia/reperfusion injury. Neutrophils from these animals are deficient at spreading, phagocytosing complement-opsonized particles, and in several Fc-mediated functions. They also exhibit impaired oxidative burst and a diminished responsiveness in LPS- and taxol-mediated gene expression.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt a region of the Itgam gene encoding the translational initiation codon and 15 amino acids of the signal peptide. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into 3.5 day C57BL/6 blastocysts and chimeric animals obtained.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Itgam^tm1Myd/Itgam^tm1Myd

        B6.129S4-Itgam^tm1Myd

• immune system phenotype
• abnormal inflammatory response (MGI Ref ID J:113463)
  • following exposure to LPS then challenge with TNF at the same site to initiate a local Shwartman response, mice fail to exhibit hemorrhage and have fewer thrombus-occluded vessels and reduced fibrin compared to the thrombohemorrhagic vasculitis observed in wild-type mice
  • however, neutrophil accumulation at the site of the Shwartman response is normal and adoptive transfer of neutrophils into a wild-type mouse elicits a normal local Shwartman response
• abnormal neutrophil morphology (MGI Ref ID J:113463)
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice
• abnormal neutrophil physiology (MGI Ref ID J:113463)
  • neutrophil degranulation after adhesion is decreased compared to in wild-type mice
• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:113463)
  • mouse serum fails to support neutrophil adhesion unlike serum from wild-type mice
• hematopoietic system phenotype
• abnormal neutrophil morphology (MGI Ref ID J:113463)
  • neutrophils that accumulate at the site of a local Shwartman response are round instead of flattened as in wild-type mice

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

Itgam^tm1Myd/Itgam^tm1Myd

        involves: 129S4/SvJae * BALB/c * C57BL/6

• cellular phenotype
• decreased apoptosis (MGI Ref ID J:38052)
  • in cultured total leukocyte populations from harvested peritoneal exudates, extravasated null neutrophils show a 56% and 45% reduction in apoptosis after 6 and 8 hours in culture respectively, compared to wild-type neutrophils
• hematopoietic system phenotype
• increased eosinophil cell number (MGI Ref ID J:38052)
  • mutants show increased eosinophil accumulation at 10.5 hours, 48 hours and 5 days in the model of peritonitis
• increased neutrophil cell number (MGI Ref ID J:38052)
  • null animals have 2-fold more neutrophils in the peritoneal exudates after 2 hours in an experimental model of peritonitis than did wild-type animals
• immune system phenotype
• abnormal leukocyte adhesion (MGI Ref ID J:38052)
  • neutrophils from null animals are significantly impaired with respect to their ability to adhere to the endothelium in response to leukotriene B4
• impaired neutrophil phagocytosis (MGI Ref ID J:38052)
  • null neurophils isolated from peritoneal lavage of thioglycollate-treated mice are unable to phagocytose complement-opsonized particles; neutrophil spreading on glass is attenuated in null neutrophils; these neutrophils also show a 60% reduction in the oxidative burst associated with phagocytosis
• increased eosinophil cell number (MGI Ref ID J:38052)
  • mutants show increased eosinophil accumulation at 10.5 hours, 48 hours and 5 days in the model of peritonitis
• increased neutrophil cell number (MGI Ref ID J:38052)
  • null animals have 2-fold more neutrophils in the peritoneal exudates after 2 hours in an experimental model of peritonitis than did wild-type animals

Itgam^tm1Myd/Itgam^tm1Myd

        involves: 129S4/SvJae * C57BL/6

• nervous system phenotype
• decreased cerebral infarction size (MGI Ref ID J:103873)
  • after 3 hours of focal ischemia and 21 hours of reperfusion, infarct volume in wild-type mice is 79.4 cubic mm versus 58.9 cubic mm in homozygous animals (26% reduction in tissue injury)
• hematopoietic system phenotype
• decreased neutrophil cell number (MGI Ref ID J:103873)
  • reduction in infarct size is accompanied by a 50% reduction in neutrophils in the periphery of the infarct area, although this is not statistically significant
• immune system phenotype
• decreased neutrophil cell number (MGI Ref ID J:103873)
  • reduction in infarct size is accompanied by a 50% reduction in neutrophils in the periphery of the infarct area, although this is not statistically significant
• homeostasis/metabolism phenotype
• decreased cerebral infarction size (MGI Ref ID J:103873)
  • after 3 hours of focal ischemia and 21 hours of reperfusion, infarct volume in wild-type mice is 79.4 cubic mm versus 58.9 cubic mm in homozygous animals (26% reduction in tissue injury)

View Research Applications

Research Applications

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

Itgam^tm1Myd related

Cell Biology Research
Defects in Cell Adhesion Molecules

Diabetes and Obesity Research
Obesity Without Diabetes (adult onset)

Immunology and Inflammation Research
Inflammation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Itgamtm1Myd
Allele Name		targeted mutation 1, Tanya N Mayadas
Allele Type		Targeted (knock-out)
Common Name(s)		CD11b/CD18 deficiency; CR3-; Cd11b-; Itgamtm1Tmn; Mac-1-;
Mutation Made By		Tanya Mayadas,   Brigham and Women's Hosp/Harvard Med Sch
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Itgam, integrin alpha M
Chromosome		7
Gene Common Name(s)		CD11B; CD11B (p170); CD11b/CD18; CR3; CR3A; F730045J24Rik; Ly-40; MAC-1; MAC1A; MGC117044; MO1A; Mac-1 alpha; Mac-1a; RIKEN cDNA F730045J24 gene; SLEB6; complement component receptor 3 alpha; complement receptor type 3; lymphocyte antigen 40; macrophage antigen alpha chain (integrin);
Molecular Note		Replacement of the exon encoding the translational initiation codon and 15 amino acids of the signal peptide with a neomycin cassette. [MGI Ref ID J:38052]

Genotyping

Genotyping Information

Genotyping Protocols

Itgam^tm1Myd, SEP PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Coxon A; Rieu P; Barkalow FJ; Askari S; Sharpe AH; von Andrian UH; Arnaout MA; Mayadas TN. 1996. A novel role for the beta 2 integrin CD11b/CD18 in neutrophil apoptosis: a homeostatic mechanism in inflammation. Immunity 5(6):653-66. [PubMed: 8986723]  [MGI Ref ID J:38052]

Additional References

Dong ZM; Gutierrez-Ramos JC; Coxon A; Mayadas TN; Wagner DD. 1997. A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci U S A 94(14):7526-30. [PubMed: 9207125]  [MGI Ref ID J:41751]

Hu C; Mayadas-Norton T; Tanaka K; Chan J; Salgame P. 2000. Mycobacterium tuberculosis infection in complement receptor 3-deficient mice. J Immunol 165(5):2596-602. [PubMed: 10946287]  [MGI Ref ID J:64055]

Perera PY; Mayadas TN; Takeuchi O; Akira S; Zaks-Zilberman M; Goyert SM; Vogel SN. 2001. CD11b/CD18 acts in concert with CD14 and toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression J Immunol 166(1):574-81. [PubMed: 11123339]  [MGI Ref ID J:66435]

Tang T; Rosenkranz A; Assmann KJM; Goodman MJ; Gutierrez-Ramos JC ; Carroll MC ; Cotran RS ; Mayadas TN. 1997. A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis. J Exp Med 186(11):1853-63. [PubMed: 9382884]  [MGI Ref ID J:44403]

van Spriel AB; Leusen JH; van Egmond M; Dijkman HB; Assmann KJ; Mayadas TN; van de Winkel JG. 2001. Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation. Blood 97(8):2478-86. [PubMed: 11290613]  [MGI Ref ID J:68805]

Itgam^tm1Myd related

Bhat N; Perera PY; Carboni JM; Blanco J; Golenbock DT; Mayadas TN; Vogel SN. 1999. Use of a photoactivatable taxol analogue to identify unique cellular targets in murine macrophages: identification of murine CD18 as a major taxol-binding protein and a role for Mac-1 in taxol-induced gene expression. J Immunol 162(12):7335-42. [PubMed: 10358184]  [MGI Ref ID J:55525]

Brandhorst TT; Wuthrich M; Finkel-Jimenez B; Warner T; Klein BS. 2004. Exploiting type 3 complement receptor for TNF-alpha suppression, immune evasion, and progressive pulmonary fungal infection. J Immunol 173(12):7444-53. [PubMed: 15585870]  [MGI Ref ID J:94857]

Bullard DC; Hu X; Schoeb TR; Axtell RC; Raman C; Barnum SR. 2005. Critical requirement of CD11b (Mac-1) on T cells and accessory cells for development of experimental autoimmune encephalomyelitis. J Immunol 175(10):6327-33. [PubMed: 16272284]  [MGI Ref ID J:119354]

Coxon A; Tang T; Mayadas TN. 1999. Cytokine-activated endothelial cells delay neutrophil apoptosis in vitro and in vivo. A role for granulocyte/macrophage colony-stimulating factor. J Exp Med 190(7):923-34. [PubMed: 10510082]  [MGI Ref ID J:115089]

Cramer DE; Allendorf DJ; Baran JT; Hansen R; Marroquin J; Li B; Ratajczak J; Ratajczak MZ; Yan J. 2006. Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury. Blood 107(2):835-40. [PubMed: 16179370]  [MGI Ref ID J:126628]

Dong ZM; Gutierrez-Ramos JC; Coxon A; Mayadas TN; Wagner DD. 1997. A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci U S A 94(14):7526-30. [PubMed: 9207125]  [MGI Ref ID J:41751]

Guerau-de-Arellano M; Alroy J; Bullard D; Huber BT. 2005. Aggravated Lyme carditis in CD11a-/- and CD11c-/- mice. Infect Immun 73(11):7637-43. [PubMed: 16239568]  [MGI Ref ID J:104290]

Hajishengallis G; Wang M; Bagby GJ; Nelson S. 2008. Importance of TLR2 in early innate immune response to acute pulmonary infection with Porphyromonas gingivalis in mice. J Immunol 181(6):4141-9. [PubMed: 18768871]  [MGI Ref ID J:139089]

Henneke P; Takeuchi O; Malley R; Lien E; Ingalls RR; Freeman MW; Mayadas T; Nizet V; Akira S; Kasper DL; Golenbock DT. 2002. Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways. J Immunol 169(7):3970-7. [PubMed: 12244198]  [MGI Ref ID J:120215]

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]

Hoffmeister KM; Felbinger TW; Falet H; Denis CV; Bergmeier W; Mayadas TN; von Andrian UH; Wagner DD; Stossel TP; Hartwig JH. 2003. The clearance mechanism of chilled blood platelets. Cell 112(1):87-97. [PubMed: 12526796]  [MGI Ref ID J:107707]

Hong F; Hansen RD; Yan J; Allendorf DJ; Baran JT; Ostroff GR; Ross GD. 2003. Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. Cancer Res 63(24):9023-31. [PubMed: 14695221]  [MGI Ref ID J:87069]

Hu C; Mayadas-Norton T; Tanaka K; Chan J; Salgame P. 2000. Mycobacterium tuberculosis infection in complement receptor 3-deficient mice. J Immunol 165(5):2596-602. [PubMed: 10946287]  [MGI Ref ID J:64055]

Hu X; Zhang D; Pang H; Caudle WM; Li Y; Gao H; Liu Y; Qian L; Wilson B; Di Monte DA; Ali SF; Zhang J; Block ML; Hong JS. 2008. Macrophage antigen complex-1 mediates reactive microgliosis and progressive dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. J Immunol 181(10):7194-204. [PubMed: 18981141]  [MGI Ref ID J:140934]

Imai M; Landen C; Ohta R; Cheung NK; Tomlinson S. 2005. Complement-mediated mechanisms in anti-GD2 monoclonal antibody therapy of murine metastatic cancer. Cancer Res 65(22):10562-8. [PubMed: 16288049]  [MGI Ref ID J:103401]

Ip WK; Takahashi K; Moore KJ; Stuart LM; Ezekowitz RA. 2008. Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome. J Exp Med 205(1):169-81. [PubMed: 18180310]  [MGI Ref ID J:131122]

Ji H; Ohmura K; Mahmood U; Lee DM; Hofhuis FM; Boackle SA; Takahashi K; Holers VM; Walport M; Gerard C; Ezekowitz A; Carroll MC; Brenner M; Weissleder R; Verbeek JS; Duchatelle V; Degott C; Benoist C; Mathis D. 2002. Arthritis critically dependent on innate immune system players. Immunity 16(2):157-68. [PubMed: 11869678]  [MGI Ref ID J:74720]

Kim DD; Miwa T; Kimura Y; Schwendener RA; van Lookeren Campagne M; Song WC. 2008. Deficiency of decay-accelerating factor and complement receptor 1-related gene/protein y on murine platelets leads to complement-dependent clearance by the macrophage phagocytic receptor CRIg. Blood 112(4):1109-19. [PubMed: 18524992]  [MGI Ref ID J:138410]

Kirimanjeswara GS; Mann PB; Pilione M; Kennett MJ; Harvill ET. 2005. The complex mechanism of antibody-mediated clearance of Bordetella from the lungs requires TLR4. J Immunol 175(11):7504-11. [PubMed: 16301658]  [MGI Ref ID J:122156]

Liu Z; Zhao M; Li N; Diaz LA; Mayadas TN. 2006. Differential roles for beta2 integrins in experimental autoimmune bullous pemphigoid. Blood 107(3):1063-9. [PubMed: 16234355]  [MGI Ref ID J:127587]

Nakazawa T; Nakazawa C; Matsubara A; Noda K; Hisatomi T; She H; Michaud N; Hafezi-Moghadam A; Miller JW; Benowitz LI. 2006. Tumor necrosis factor-alpha mediates oligodendrocyte death and delayed retinal ganglion cell loss in a mouse model of glaucoma. J Neurosci 26(49):12633-41. [PubMed: 17151265]  [MGI Ref ID J:116761]

Paul R; Obermaier B; Van Ziffle J; Angele B; Pfister HW; Lowell CA; Koedel U. 2008. Myeloid Src kinases regulate phagocytosis and oxidative burst in pneumococcal meningitis by activating NADPH oxidase. J Leukoc Biol 84(4):1141-50. [PubMed: 18625913]  [MGI Ref ID J:140230]

Perera PY; Mayadas TN; Takeuchi O; Akira S; Zaks-Zilberman M; Goyert SM; Vogel SN. 2001. CD11b/CD18 acts in concert with CD14 and toll-like receptor (TLR) 4 to elicit full lipopolysaccharide and taxol-inducible gene expression J Immunol 166(1):574-81. [PubMed: 11123339]  [MGI Ref ID J:66435]

Pilione MR; Agosto LM; Kennett MJ; Harvill ET. 2006. CD11b is required for the resolution of inflammation induced by Bordetella bronchiseptica respiratory infection. Cell Microbiol 8(5):758-68. [PubMed: 16611225]  [MGI Ref ID J:135740]

Rooyakkers AW; Stokes RW. 2005. Absence of complement receptor 3 results in reduced binding and ingestion of Mycobacterium tuberculosis but has no significant effect on the induction of reactive oxygen and nitrogen intermediates or on the survival of the bacteria in resident and interferon-gamma activated macrophages. Microb Pathog 39(3):57-67. [PubMed: 16084683]  [MGI Ref ID J:106398]

Rosenkranz AR; Coxon A; Maurer M; Gurish MF; Austen KF; Friend DS; Galli SJ; Mayadas TN. 1998. Impaired mast cell development and innate immunity in Mac-1 (CD11b/CD18, CR3)-deficient mice. J Immunol 161(12):6463-7. [PubMed: 9862668]  [MGI Ref ID J:52128]

Soriano SG; Coxon A; Wang YF; Frosch MP; Lipton SA; Hickey PR; Mayadas TN. 1999. Mice deficient in Mac-1 (CD11b/CD18) are less susceptible to cerebral ischemia/reperfusion injury. Stroke 30(1):134-9. [PubMed: 9880401]  [MGI Ref ID J:103873]

Tang T; Rosenkranz A; Assmann KJM; Goodman MJ; Gutierrez-Ramos JC ; Carroll MC ; Cotran RS ; Mayadas TN. 1997. A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis. J Exp Med 186(11):1853-63. [PubMed: 9382884]  [MGI Ref ID J:44403]

Utomo A; Hirahashi J; Mekala D; Asano K; Glogauer M; Cullere X; Mayadas TN. 2008. Requirement for Vav proteins in post-recruitment neutrophil cytotoxicity in IgG but not complement C3-dependent injury. J Immunol 180(9):6279-87. [PubMed: 18424751]  [MGI Ref ID J:134524]

Wakselman S; Bechade C; Roumier A; Bernard D; Triller A; Bessis A. 2008. Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci 28(32):8138-43. [PubMed: 18685038]  [MGI Ref ID J:140167]

Wolfe DN; Kirimanjeswara GS; Harvill ET. 2005. Clearance of Bordetella parapertussis from the lower respiratory tract requires humoral and cellular immunity. Infect Immun 73(10):6508-13. [PubMed: 16177324]  [MGI Ref ID J:104212]

Yan J; Vetvicka V; Xia Y; Coxon A; Carroll MC; Mayadas TN; Ross GD. 1999. Beta-glucan, a 'specific' biologic response modifier that uses antibodies to target tumors for cytotoxic recognition by leukocyte complement receptor type 3 (CD11b/CD18). J Immunol 163(6):3045-52. [PubMed: 10477568]  [MGI Ref ID J:57602]

Zaltzman R; Alexandrovich A; Trembovler V; Shohami E; Gozes I. 2005. The influence of the peptide NAP on Mac-1-deficient mice following closed head injury. Peptides 26(8):1520-7. [PubMed: 16042992]  [MGI Ref ID J:106672]

Zhang B; Hirahashi J; Cullere X; Mayadas TN. 2003. Elucidation of molecular events leading to neutrophil apoptosis following phagocytosis: cross-talk between caspase 8, reactive oxygen species, and MAPK/ERK activation. J Biol Chem 278(31):28443-54. [PubMed: 12736263]  [MGI Ref ID J:120441]

van Spriel AB; Leusen JH; van Egmond M; Dijkman HB; Assmann KJ; Mayadas TN; van de Winkel JG. 2001. Mac-1 (CD11b/CD18) is essential for Fc receptor-mediated neutrophil cytotoxicity and immunologic synapse formation. Blood 97(8):2478-86. [PubMed: 11290613]  [MGI Ref ID J:68805]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This strain originated on a B6;129S4 background and has been backcrossed to C57BL/6 for at least ten generations. When maintaining a homozygous colony, the donating investigator advises replacing breeders every six months with the offspring from heterozygous matings, avoiding sibling matings. Coat color expected from breeding:Black
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K20

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Fax: 207.288.6150
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phone:	207-288-6470
fax:	207-288-6655

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