NOD.Cg-Myd88^tm1Defr H2^b/JkraJ

Stock number: 039017
Product name: NOD.B10Myd88^fl/fl
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

NOD.B10Myd88^fl mice carry an Myd88 allele with a floxed exon 3 that was backcrossed onto a NOD.B10 genetic background (Stock No. 002591). This congenic strain has the MHC H2^b haplotype from the C57BL/10SnJ strain with mice exhibiting some but not all of the immune dysfunctions of NOD/LtJ (Stock No. 001976) mice. These mice may be useful for generating conditional Myd88 mutants when studying MYD88-TLR signaling pathways in various inflammatory and autoimmune diseases.

Note, the same Myd88 floxed allele is available on a congenic C57BL/6 background as Stock No. 008888.

Detailed description

Myeloid differentiation primary response gene 88 (MyD88) codes for a cytosolic adapter protein that is essential in signal transduction of the toll-like receptor (TLR) signaling pathway involved in innate and adaptive immune responses. Myd88 mutations have been linked to autoimmune diseases such as lupus, multiple sclerosis (MS) and Sjögren's syndrome (SS).

These NOD.B10Myd88^fl mice carry an Myd88 allele with a floxed exon 3 on a NOD.B10 genetic background (Stock No. 002591). The NOD.B10 (or NOD.H2-b) strain has the MHC H2^b haplotype from the C57BL/10SnJ strain with mice exhibiting some but not all of the immune dysfunctions of NOD/LtJ (Stock No. 001976) mice. Female mice of this strain do not develop diabetes insulitis, cyclophosphamide-induced diabetes or spontaneous diabetes, but do develop lymphocytic infiltrates in the kidneys, lungs, lacrimal glands, and the submandibular glands as well as other SS pathologies ~26 weeks of age.

Homozygous NOD.B10Myd88^fl/fl mice are viable and fertile. NOD.B10Myd88^fl mice may be useful for generating conditional Myd88 mutants when studying the role of MYD88-TLR signaling in autoimmune and inflammatory diseases.

Note, the same Myd88 floxed allele is available on a congenic C57BL/6 background as Stock No. 008888.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these NOD.B10 congenic mice could vary from that originally described on a C57BL/6 genetic background. We may modify the strain description if necessary, as published results become available.

Development

The NOD.B10Myd88^fl mouse model was generated by backcrossing the C57BL6-congenic Myd88 floxed allele (Stock No. 008888) onto the NOD.B10 genetic background (Stock No. 002591).

The NOD.B10, or NOD.H2-b, congenic mouse line was made by transferring the H2b haplotype from C57BL/10SnJ (Stock No. 000666) mice to the NOD/Lt (Stock No. 001976) strain.

The Myd88^fl allele was designed by Dr. Anthony L. DeFranco (University of California San Francisco) to have loxP sites flanking exon 3 of the myeloid differentiation primary response gene 88 (Myd88) on chromosome 9. Specifically, the targeting vector placed a frt-flanked neomycin resistance cassette and loxP site upstream of exon 3, and a second loxP site just downstream of exon 3 of the myeloid differentiation primary response gene 88 locus (Myd88) on chromosome 9. The construct was electroporated into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric animals were bred with Actin-FLPe mice (on a C57BL/6 congenic background; see Stock No. 005703) to achieve germline transmission and to remove the neo cassette. The resulting Myd88^fl mice (retaining the loxP site flanked exon 3 and a single residual frt site) were then backcrossed to C57BL/6J for 11 generations (and the Flpe-expressing transgene was removed) prior to sending heterozygous males with black coat color to The Jackson Laboratory Repository in 2009. The C57BL/6-congenic Myd88 floxed colony is Stock No. 008888.

Dr. Jill M. Kramer acquired some Stock No. 008888 animals, on the C57BL/6 congenic background, and then backcrossed them to NOD.B10 mice (Stock No. 002591) for at least 5 generations using The Jackson Laboratory speed congenic protocol. The resulting NOD.B10-congenic strain is Stock No. 039017 NOD.Cg-Myd88^tm1Defr H2^b/JkraJ. To establish our live colony, an aliquot of frozen sperm was used to fertilize NOD/ShiLtJ (Stock No. 001976) oocytes.

Allele

Symbol: H2^b
Name: b variant
MGI accession ID: MGI:3579319
Generation method: Not Applicable
Marker symbol: H2
Marker name: histocompatibility-2, MHC
Marker synonyms: H-2; MHC-II
Chromosome: 17
Strain of origin: Not Applicable
General note: The b variant has been observed in the following strains: C57BL/10, C57BL/10SnJ, BXSB/MpJ, C57BL/6J, C57L/J, LP/J, 129P3/J, 129P1/ReJ.

Allele

Symbol: Myd88^tm1Defr
Name: targeted mutation 1, Anthony L DeFranco
MGI accession ID: MGI:3809600
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Myd88^fl
Marker symbol: Myd88
Marker name: myeloid differentiation primary response gene 88
Marker synonyms: IMD68; MYD88D; WM1
Chromosome: 9
Strain of origin: 129P2/OlaHsd
Molecular note: Exon 3 was flanked by loxP sites by placing a FRT-flanked neo-cassette with a 3' loxP site upstream of exon 3 with an additional loxP site being placed downstream of exon 3. Founders were crossed with ACTB-FLPe mice to remove the neo selection cassette. Expression levels of Myd88 were unaffected by loxP insertion. Cre-recombination is predicted to excise exon 3 and create a null allele.