BXSB.129S2(B6)-Ighm^tm1Cgn/DcrJ

Stock number: 021871
Strain synonyms: BXSB.Ighm-/-, BXSB.Yaa Ighm-/-, Ighm-deficient BXSB.Yaa, BXSB.Ighm null, BXSB.Cmu-, BXSB.muMT-, BXSB.IgM-
Research areas: Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Research Tools

Description

Ighm-deficient BXSB.Yaa mice (BXSB.Ighm-/- or BXSB.Yaa Ighm-/-) are a BXSB/MpJ-congenic strain carrying a null mutation of the immunoglobulin heavy chain of the class mu. The mature B cell-deficiency of BXSB.Ighm-/- mice prevents manifestation of the spontaneous lupus-like autoimmune syndrome observed for BXSB/MpJ inbred mice. These BXSB.Ighm-/- mice may be useful in studying the role of B cells in autoimmune disease, and other mechanisms that are not B cell-dependent (e.g., dendritic cells and T cells).

Detailed description

Ighm-deficient BXSB.Yaa mice (BXSB.Ighm-/- or BXSB.Yaa Ighm-/-) are a BXSB/MpJ-congenic strain carrying a null mutation of the immunoglobulin heavy chain of the class mu.

BXSB/MpJ inbred males (Stock No. 000740) develop a spontaneous lupus-like autoimmune syndrome: mortality starts at ~13 weeks of age with 50% lethality by ~30 weeks and 76% lethality by ~40 weeks. BXSB/MpJ inbred females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

Homozygous (Ighm-/-) mice are viable and fertile. Homozygotes lack mature B cells and have no expression of membrane-bound IgM; although some B cells may be produced using immunoglobulin genes other than mu. As such, they should be maintained in pathogen-free conditions on sulfatrim water to increase colony health (similar to other immunodeficient strains). Compared to BXSB/MpJ, the mature B cell-deficiency of BXSB.Ighm-/- mice prevents manifestation of the spontaneous autoimmune phenotype in both males and females.

Heterozygous males (BXSB.Ighm+/-) develop the BXSB/MpJ autoimmune phenotype. Heterozygous females develop a greatly attenuated form of autoimmune disease because they lack Yaa.

C57BL/6J-congenic mice harboring this Ighm null allele are described and available from The Jackson Laboratory Repository as Stock No. 002288.

Development

The Ighm null allele (Cμ-, μMT-, IgM-, or Ighm^tm1Cgn) was designed by Dr. Klaus Rajewsky (University of Cologne) with a neomycin resistance cassette disrupting one of the membrane exons of the Ighm gene (immunoglobulin heavy constant mu) on chromosome 12. C57BL/6J-congenic mice harboring this Ighm null allele are described and available from The Jackson Laboratory Repository as Stock No. 002288.
Dr. Derry C. Roopenian (The Jackson Laboratory) obtained some of these mutant mice and backcrossed them with BXSB/MpJ inbred mice (Stock No. 000740) for 12 generations, and then maintained the colony by breeding homozygous mice together. In 2013, Dr. Roopenian sent some BXSB.Yaa Ighm-/- mice at generation N12F12 to The Jackson Laboratory Repository (Autoimmune Resource) to establish Stock No. 021871. Male mice have the BXSB/MpJ-derived Y chromosome that contains the Y-linked autoimmune accelerator locus (Yaa).

Allele

Symbol: Ighm^tm1Cgn
Name: targeted mutation 1, University of Cologne
MGI accession ID: MGI:1857187
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ighm
Marker name: immunoglobulin heavy constant mu
Chromosome: 12
Strain of origin: 129S2/SvPas
Molecular note: A neomycin resistance cassette disrupted one of the membrane exons of the gene encoding immunoglobulin heavy chain of the class mu (IgM).