These Ighm knock-out mice are unable to produce the secreted form of Ighmtm1Che and exhibit an increase in B-1 lymphocytes in the spleen and peritoneum.
Jianzhu Chen, MIT Center for Cancer Research
Mice homozygous for the Ighmtm1Che allele are viable, fertile and exhibit no apparent defects. While membrane expressed Ighmtm1Che is unhindered, these mice are unable to produce the secreted form of Ighmtm1Che. Increases in some classes of serum Ig is noted in young animals (IgA, IgG2a and IgG3), but these differences are largely absent in the adult animals. The IgG1 antibody response to suboptimal doses of a T cell-dependent antigen is impaired. Conversely, the IgG2a antibody response to a T cell-independent antigen appears augmented. An approximately three-fold increase in B-1 lymphocytes is noted in the spleen and peritoneum.
A targeting vector containing the neomycin resistance and thymidine kinase genes was used to disrupt the mouse Ighm gene such that the mu-secreted exon and its three downstream polyadenylation sites are replaced by a cDNA encoding the Cmu-4 exon and the mu-membrane exon. The resulting configuration results in the exclusive expression of the membrane form of Ighm at the expense of the secreted form. The targeting construct was transfected into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Selected ES cells were injected into C57BL/6 blastocysts. This strain originated on a B6;129S background.
|Allele Name||targeted mutation 1, Jianzhu Chen|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||muS-; secreted IgM-; sIgM-; Smu-|
|Gene Symbol and Name||Ighm, immunoglobulin heavy constant mu|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A targeting vector was constructed in which the exon encoding the secreted form of the immunoglobulin mu (IgM) heavy chain and its three downstream poly(A) sites were replaced by a cDNA fragment encoding the constant region mu4 exon and the exon encoding the membrane-bound form of IgM. The resultant homozygous mutant mice had B cells that did not secrete IgM, but did express membrane-bound IgM.|
Heterozygotes and homozygotes are viable and fertile. Homozygous mice are more susceptible to pathogenic bacteria, so conventional specific pathogen-free (SPF) conditions are recommended.
When using the B6;129S4-Ighmtm1Che/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003751 in your Materials and Methods section.