C57BL/6J-Del(12Ighg3-Ighg2b)1Mzeng/J

Stock number: 038643
Product name: IgG KO

Research areas: Immunology, Inflammation and Autoimmunity Research

Description

IgG knock-out mice have an 80 kbp deletion that removes the IgG isotypes (Ighg1, Ighg2a, Ighg2b, and Ighg3). Homozygous mice develop an altered gut microbiome that promotes differentiation of IL17A-producing δγ T cells. This strain may be useful for research involving enteric pathogens and the gut microbiome.

Detailed description

Ighg (immunoglobulin heavy chain [gamma polypeptide]) genes encode proteins that are involved in activation of the immune response through recognition of foreign antigens.

IgG knockout mice carry a CRISPR/cas9 generated 80kbp deletion, which removes all genes downstream of Ighg3 and upstream of Ighg2b (Ighg1, Ighg2a, Ighg2b, and Ighg3). ELISA analysis of fecal pellets indicates loss of serum IgG isotypes, but normal levels of serum IgA, IgE, and IgM. Homozygous IgG KO neonates (P7 and P14) exhibit increased susceptibility to enteric infection by Citrobacter rodentium, increased gut barrier permeability, and intestinal inflammation due to loss of maternal IgG antibodies in the neonatal gut. IgG deficiency in neonates (using IgG KO dams) alters the gut microbiome by promoting differentiation of IL17A-producing δγ T cells in the small intestine and colon, which continues through adulthood and contributes to increased disease severity in DSS-induced colitis. Homozygous mice are viable and fertile.

Development

CRISPR/cas9 genome editing was used to delete the IgG region (approx. 80kbp) encompassing 1 kb upstream of Ighg3 and 1 kb downstream of Ighg2b of the mouse genome on chromosome 12. The deletion removed Ighg1, Ighg2a, Ighg2b, and Ighg3. sgRNAs, Cas9 endonuclease, and donor ssDNA were introduced into C57BL/6J-derived zygotes. Embryos were transferred to pseudopregnant females, and correctly targeted pups were bred to C57BL/6 mice for germline transmission. Sanger sequencing was used to confirm the deletion. Mice have been crossed to C57BL/6 for at least 10 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Allele

Symbol: Del(12Ighg3-Ighg2b)1Mzeng
Name: deletion, Chr 12, Melody Zeng 1
MGI accession ID: MGI:7518234
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Synonyms: IgG KO
Marker symbol: Del(12Ighg3-Ighg2b)1Mzeng
Marker name: deletion, Chr 12, Melody Zeng 1
Chromosome: 12
Strain of origin: C57BL/6J
Molecular note: CRISPR/cas9 genome editing is used to delete the IgG region (approx. 80kbp) encompassing 1 kb upstream of Ighg3 and 1 kb downstream of Ighg2b. The deletion removed Ighg1, Ighg2a, Ighg2b, and Ighg3.