Description

Strain Information

Former Names B6.129S1-Csf2rb1tm1Cgb/J    (Changed: 26-JUN-07 ) 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 ?+F4 (08-JAN-08)   Donating Investigator Lorraine Robb,   The Walter and ElizaHall Institute

Description
Homozygous mice are viable and fertile with no behavioral abnormalities. In response to GM-CSF, bone marrow and splenocytes from homozygous mice fail to exhibit proliferation, enhanced survival in vitro, or synergistic interaction with M-CSF. They also fail to proliferate in response to IL-5. IL-3 binding and responses are unaffected. Cell composition in thymus, spleen, bone marrow, and lymph node is not significantly altered. Circulating eosinophils are dramatically reduced in blood with lesser reduction in bone marrow and tissues. Homozygous mice develop pulmonary peribronchovascular lymphoid infiltrates and areas resembling pulmonary alveolar proteinosis (PAP). Consistent with this, mutant mice have greatly increased surfactant protein-B and D accumulation in lung/airway tissue, no attenuation of saturated phosphatidylcholine with advancing age, and high levels of GM-CSF in bronchoaveolar lavage fluid. Homozygous mice are resistant to intradermal Leishmania major infection and peritoneal macrophages infected in vitro or in vivo are similarly resistant with a more activated phenotype and increased nitric oxide production than wildtype. Homozygous mice have reduced numbers of resident Langerhans cells in epidermis with significantly impaired recovery of this population following topical LPS treatment. This mutant is a model for PAP and may also be useful in studies of lung physiology and disease, surfactant homeostasis and metabolism, innate immunity, cytokine signaling, myoproliferative disease, hematopoietic cell populations requiring GM-CSF or IL-5 for development and function, and models of ischemic, traumatic, toxic, and inflammatory injuries.

Development
A targeting vector designed to insert a Neo cassette into exon 7 of the endogenous gene was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric mice were bred with C57BL/6. Heterozygous mice were backcrossed 10 generations to C57BL/6 before arriving at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Csf2rb

005963

B6.129S1-Csf2rb2tm1Cgb Csf2rbtm1Clsc/J

View Strains carrying other alleles of Csf2rb     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Csf2rb^tm1Cgb/Csf2rb^tm1Cgb

        involves: 129S1/Sv * C57BL/6

• hematopoietic system phenotype
• abnormal myeloblast morphology/development (MGI Ref ID J:29737)
  • in clonal cultures of mutant bone marrow cells, even high concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5 fail to stimulate colony formation, but cells show normal responsiveness to stimulation by IL-3 and other growth factors
• decreased eosinophil cell number (MGI Ref ID J:29737)
  • eosinophil numbers in the peripheral blood and bone marrow are reduced by 95%
• immune system phenotype
• decreased eosinophil cell number (MGI Ref ID J:29737)
  • eosinophil numbers in the peripheral blood and bone marrow are reduced by 95%
• lung inflammation (MGI Ref ID J:29737)
  • develop pulmonary peribronchovascular lymphoid infiltrates and intraalveolar eosinophilic material and foamy macrophages are present
• respiratory system phenotype
• abnormal respiratory alveoli morphology (MGI Ref ID J:29737)
  • mutants exhibit areas resembling alveolar proteinosis
• lung inflammation (MGI Ref ID J:29737)
  • develop pulmonary peribronchovascular lymphoid infiltrates and intraalveolar eosinophilic material and foamy macrophages are present

View Research Applications

Research Applications

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

Cardiovascular Research
Ischemia studies
Vascular Defects (defective macrophage function)

Hematological Research
Hematopoietic Defects
Immunological Defects

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

Internal/Organ Research
Lung Defects
Wound Healing

Research Tools
Immunology and Inflammation Research (Macrophage Deficiency)
Toxicology Research (free radical research)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Csf2rbtm1Cgb
Allele Name		targeted mutation 1, C Glenn Begley
Allele Type		Targeted (knock-out)
Common Name(s)		Beta-c-;
Mutation Made By		Glenn Begley,   Amgen
Strain of Origin		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
ES Cell Line Name		W9.5/W95
ES Cell Line Strain		129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name		Csf2rb, colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage)
Chromosome		15
Gene Common Name(s)		AI848964; AIC2B; Bc; CD131; CDw131; Csf2rb1; Csfgmrb; IL3RB; IL5RB; Il3r; Il3rb; Il3rb1; Il5rb; beta c; colony stimulating factor 2 receptor, beta 1, low-affinity (granulocyte-macrophage); colony stimulating factor, granulocyte macrophage receptor, beta chain; common beta chain; expressed sequence AI848964; interleukin 3 receptor beta chain; interleukin 3 receptor, beta chain 1; interleukin 5 receptor beta;
Molecular Note		Exon 7 was disrupted by the insertion of a neomycin selection cassette that introduced stop codons into all three reading frames. A binding assay of homozygous bone marrow cells showed that high affinity binding of the colony stimulating factor was ablated. Binding of interleukin 3 was unaffected in cells isolated from mutant mice, indicating that the homologous interleukin 3 receptor was not affected by the targeting event. [MGI Ref ID J:29737]

Genotyping

Genotyping Information

Genotyping Protocols

Csf2rb^tm1Cgb, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Robb L; Drinkwater CC; Metcalf D; Li R; Kontgen F; Nicola NA; Begley CG. 1995. Hematopoietic and lung abnormalities in mice with a null mutation of the common beta subunit of the receptors for granulocyte-macrophage colony-stimulating factor and interleukins 3 and 5. Proc Natl Acad Sci U S A 92(21):9565-9. [PubMed: 7568173]  [MGI Ref ID J:29737]

Additional References

Csf2rb^tm1Cgb related

Gillessen S; Mach N; Small C; Mihm M; Dranoff G. 2001. Overlapping roles for granulocyte-macrophage colony-stimulating factor and interleukin-3 in eosinophil homeostasis and contact hypersensitivity. Blood 97(4):922-8. [PubMed: 11159518]  [MGI Ref ID J:67404]

Reed JA; Ikegami M; Robb L; Begley CG; Ross G; Whitsett JA. 2000. Distinct changes in pulmonary surfactant homeostasis in common beta-chain- and GM-CSF-deficient mice. Am J Physiol Lung Cell Mol Physiol 278(6):L1164-71. [PubMed: 10835321]  [MGI Ref ID J:77217]

Roberts AW; Foote S; Alexander WS; Scott C; Robb L; Metcalf D. 1997. Genetic influences determining progenitor cell mobilization and leukocytosis induced by granulocyte colony-stimulating factor. Blood 89(8):2736-44. [PubMed: 9108391]  [MGI Ref ID J:40267]

Scott CL; Robb L; Mansfield R; Alexander WS; Begley CG. 2000. Granulocyte-macrophage colony-stimulating factor is not responsible for residual thrombopoiesis in mpl null mice Exp Hematol 28(9):1001-7. [PubMed: 11008012]  [MGI Ref ID J:64501]

Waskow C; Liu K; Darrasse-Jeze G; Guermonprez P; Ginhoux F; Merad M; Shengelia T; Yao K; Nussenzweig M. 2008. The receptor tyrosine kinase Flt3 is required for dendritic cell development in peripheral lymphoid tissues. Nat Immunol 9(6):676-83. [PubMed: 18469816]  [MGI Ref ID J:136209]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

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

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:	207-288-6655

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