B6;NZM-Sle1^NZM2410/Aeg Sle2^NZM2410/Aeg Sle3^NZM2410/Aeg/LmoJ

Stock number: 007228
Product name: B6.NZMSle1/Sle2/Sle3
Strain synonyms: B6.NZM-Sle1^NZM2410/Aeg Sle2^NZM2410/Aeg Sle3^NZM2410/Aeg/LmoJ
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

Mice homozygous for the NZM2410 lupus susceptibility QTL (Sle1, Sle2 and Sle3) develop a systemic autoimmunity with fatal glomerulonephritis. Mice from this strain differ from those of NZM2410/J (Stock No. 002676) in that disease onset is slightly delayed with improved breeding and survival. This strain may used in autoimmunity and lupus research.

Detailed description

Mice homozygous for three NZM2410-derived lupus susceptibility QTLs (Sle1, Sle2, Sle3) on the C57BL/6J background develop a systemic autoimmunity with fatal glomerulonephritis. One hundred percent of mice die by 12 months of age. Death occurs within days of kidney failure. In the days between kidney failure and death, the mice exhibit heavy proteinuria, elevated blood urea nitrogen and generalized edema. In comparison to NZM2410 (see Stock No. 002676), disease onset in this strain is slightly delayed. With about 6% of the NZM2410 genome, BcN/LmoJ is phenotypically similar to NZM2410, but breeding and survival are improved.

Development

Individual congenic strains for three NZM2410/J lupus susceptibility QTL (Sle1, Sle2 and Sle3) were generated by six successive backcrosses to C57BL/6J and genotyped using SSLP markers located at the terminal ends of the interval and one internal marker closely linked to the susceptibility locus for each QTL. Additional markers were used to screen each chromosome, and contaminating intervals were identified and selectively eliminated at N3, N4 and N7. Two double congenics, Sle1/Sle2 and Sle1/Sle3, were created by intercross and selection for homozygosity along both congenic intervals. The double congenics then were intercrossed and selected for homozygosity at each QTL to produce this recombinant congenic. This strain was donated to The Jackson Laboratory Repository in 2007 by Dr. Laurence Morel.

In 2013, a SNP (single nucleotide polymorphism) panel analysis, using 16 markers that distinguish C57BL/6 allele-type from NZM2410/J allele-type, was performed on the living colony at The Jackson Laboratory Repository. This showed 12/16 markers were homozygous for C57BL/6 allele-type (one marker each on chromosomes 1 [~52.0 cM], 3, 4 [~10.9 cM], 6, 8, 9, 16, and 19; two markers each on chromosomes 13 and 17). 4/16 markers were homozygous for NZM2410/J allele-type (one marker on chromosome 2 [~27.3 cM], two markers on chromosome 11 [~2.0 cM and ~9.8 cM] and one marker on chromosome 12 [~9.8 cM]). These regions of NZM2410/J are in addition to the Sle1 [chr1; ~76 cM], Sle2 [chr4; ~39 cM] and Sle3 [chr7; ~15 cM] regions selected for during backcrossing onto C57BL/6. Of note, this SNP pattern is identical to all previous SNP test results performed on the living colony at The Jackson Laboratory Repository (2011 and 2012).

In July 2019, the live colony was confirmed to have all three Sle loci as homozygous for NZM. However, one region on the proximal end of chromosome 15 formerly believed to be homozygous for NZM was discovered to be homozygous for C57BL/6J. See representative GigaMUGA results by clicking here. Stock No. 007228 is considered recombinant inbred rather than congenic. If further genome analysis is performed by The Jackson Laboratory, we may update our description accordingly.

Allele

Symbol: Sle2^NZM2410/Aeg
Name: NZM2410/Aeg
MGI accession ID: MGI:2155957
Generation method: QTL
Marker symbol: Sle2
Marker name: systemic lupus erythmatosus susceptibility 2
Chromosome: 4
Strain of origin: NZM2410/Aeg
Molecular note: This allele confers susceptibility to glomerulonephritis compared to C57BL/6J.

Allele

Symbol: Sle3^NZM2410/Aeg
Name: NZM2410/Aeg
MGI accession ID: MGI:2156753
Generation method: QTL
Marker symbol: Sle3
Marker name: systemic lupus erythmatosus susceptibility 3
Chromosome: 7
Strain of origin: NZM2410/Aeg
Molecular note: This allele confers increased serum IgM and IgG Ab levels and severe glomerulonephritis compared to C57BL/6J.

Allele

Symbol: Sle1^NZM2410/Aeg
Name: NZM2410/Aeg
MGI accession ID: MGI:2154331
Generation method: QTL
Marker symbol: Sle1
Marker name: systemic lupus erythmatosus susceptibility 1
Chromosome: 1
Strain of origin: NZM2410/Aeg