NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ

Stock number: 006608
Product name: NOD.IgHEL,Igh-/-
Strain synonyms: NOD.IgHEL.Igu, NOD.IgHEL.Igμ^null
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Mice of this strain do not express endogenous IgM, and all B lymphocytes express Ig molecules specific for hen egg lyzozyme (HEL). This strain may be used to study defects in B-cell selection as it relates to Type 1 Diabetes.

Detailed description

NOD.Cg-Ighm^tm1Cgn Tg(IghelMD4)4Ccg/DvsJ (NOD.IgHEL Ighm-deficient) mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. Because these mice are Ighm-deficient, they do not express endogenous IgM. All B lymphocytes in NOD.IgHEL Ighm-deficient mice express Ig molecules specific for hen egg lyzozyme (HEL). There is no significant difference in the total number of B and T lymphocytes between NOD.IgHEL Ighm-deficient and NOD.IgHEL (Stock No. 006345) mice. The incidence of diabetes in transgenic vs. non-transgenic NOD.Ighm-deficient mice is similar by 21 weeks of age, (16.7% vs. 13.6%, respectively). Histological evaluation of 12 week old NOD.IgHEL Ighm-deficient mice shows that most mice have low levels of insulitis compared to NOD/ShiLt control mice, although an occasional animal had extensive insulitis. In addition, NOD.IgHEL Ighm-deficient mice develop lymphosarcomas after 20 weeks of age. This pathology is not observed in either NOD.Ighm-deficient or NOD.IgHEL transgenic mice.

This strain may be used to study defects in B-cell selection as it relates to Type 1 Diabetes.

Development

NOD.129S2-Ighm^tm1Cgn/Dvs (Stock No. 003903) at generation N10 was bred with NOD.B6-Tg(IghelMD4)4Ccg/Dvs (Stock No. 004253). The doubly heterozygous offspring were backcrossed to the former strain (Stock No. 003903) to make the strain homozygous for the Ighm^tm1Cgn mutation. Siblings were then intercrossed to make this strain additionally homozygous for Tg(IghelMD4)4Ccg. In 2006, The T1DR received this strain at generation N11F16.

Allele

Symbol: Tg(IghelMD4)4Ccg
Name: transgene insertion 4, Christopher C Goodnow
MGI accession ID: MGI:2384162
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(IghelMD4)4Ccg
Marker name: transgene insertion 4, Christopher C Goodnow
Chromosome: 17
Strain of origin: C57BL/6
Expressed genes: Ighg,Immunoglobulin heavy chain (gamma polypeptide),mouse, laboratory
Molecular note: The hybridoma HyHEL10 produces an antibody with high affinity for hen egg lysozyme. Genomic clones encoding HyHEL10 immunoglobulin heavy and light chains were used for this construct. The gamma1-constant region of the heavy chain was replaced by a segment containing the mu and delta constant region genes derived from BALB/c mice. The light and heavy chains were co-injected into C57BL/6 eggs. Five lines, MD3-MD7, that carried multiple copies of the transgene construct were created. The MD4 line had the highest expression of the transgene and was propogated for further studies. Mice carrying this transgene had high serum titers of anti-lysozyme antibodies.

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).