B6.129S1-Csf2rb^tm1Cgb/J

Stock number: 005940
Product name: Βc KO
Research areas: Cardiovascular Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

These Csf2rb knock-out mice exhibit a failure of bone marrow and splenocyte cells to proliferate in response to granulocyte-macrophage colony-stimulating factor(GM-CSF). They are useful for studies of hematopoiesis.

Detailed 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.

Allele

Symbol: Csf2rb^tm1Cgb
Name: targeted mutation 1, C Glenn Begley
MGI accession ID: MGI:2181245
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Csf2rb
Marker name: colony stimulating factor 2 receptor, beta, low-affinity (granulocyte-macrophage)
Chromosome: 15
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.