Control strains for NOD/LtJ mice in diabetes research

NOD/LtJ mice (Stock No. 001976) are used extensively as a model for type I diabetes insulin-dependent diabetes mellitus (IDDM). Autoimmune insulitis, hypoinsulinemia, glycosuria, and hyperglycemia characterize diabetes in NOD/LtJ mice. Female NOD/LtJ mice housed at The Jackson Laboratory have an earlier onset and higher incidence of IDDM symptoms compared to male mice (90- 100% by 30 weeks of age in females vs. 40-60% by 30-40 weeks of age).

The generation and progression of diabetes in NOD mice can be attributed to a combination of factors under complex polygenic control. The major component of diabetes susceptibility is the unique H2^g7 MHC haplotype (K^d, A^g7, E^null, D^b).

Environmental conditions including housing, health status and diet all effect the development of disease symptoms. NOD/LtJ mice also exhibit multiple aberrant immunophenotypes including defective antigen presenting cell immunoregulatory functions, defects in the regulation of the T lymphocyte repertoire, and defective natural killer cell function.

Given the multifaceted nature of the disease symptoms in NOD/LtJ mice, choosing a diabetes-free control strain is often complicated. Selection of a control strain depends on the nature of the experiment and the hypotheses being tested.

Possible control strains include: (1) inbred strains related to NOD/LtJ; (2) NOD stocks congenic for MHC haplotypes; (3) NOD congenic strains that vary at non-MHC loci; (4) NOD congenics carrying additional mutations affecting the immunological status of the mouse; and (5) NOD transgenic strains.

Table 1: NOD/LtJ control strains, their characteristics, and their potential uses

RELATED INBRED STRAINS

STRAIN NAME: ALR/LtJ
STOCK NO.:  003070
MHC HAPLOTYPE: H2^gx (K^d, A^g7, E^null, D^x)
CHARACTERISTICS AND USES: Alloxan-induced diabetes-resistance; closely related to NOD; MHC very similar to NOD (unique H2-D^x variant); useful as a closely related insulitis and diabetes free.

STRAIN NAME: ALS/LtJ
STOCK NO.: 003072
MHC HAPLOTYPE: H2^nb1 (K^d, A^nb1, E^k, D^b)
CHARACTERISTICS AND USES: Alloxan-induced diabetes-susceptible; closely related to NON/LtJ mice; exhibit impaired glucose tolerance; males develop hyperinsulinemia with age; mice contain genes predisposing them to both type I and type II diabetes.

STRAIN NAME: NON/LtJ
STOCK NO.: 002423
MHC HAPLOTYPE: H2^nb1 (K^b, A^nb1, E^k, D^b)
CHARACTERISTICS AND USES: Closely related to NOD; diabetes-resistant MHC; exhibit some autoimmune immunological abnormalities; develop obesity and impaired glucose tolerance; useful for genetic analysis of diabetes susceptibility genes.

STRAIN NAME: NOR/LtJ
STOCK NO.: 002050
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Contains portions of C57BLKS/J genome; same MHC as NOD/LtJ; insulitis resistant and diabetes free; useful for islet isolation and examining the role of non-MHC genes in development of diabetes.

STRAIN NAME: SJL/J
STOCK NO.: 000686
MHC HAPLOTYPE: H2^s (K^s, A^s, E^s, D^s)
CHARACTERISTICS AND USES: Both NOD and SJL/J are derived from swiss mice; immuno-competent but have elevated levels of circulating T cells; useful as control when studying immune defects in NOD/LtJ mice.

STRAIN NAME: SWR/J
STOCK NO.: 000689
MHC HAPLOTYPE: H2^q (K^q, A^q, E^q, D^q)
CHARACTERISTICS AND USES: Both NOD and SWR/J are derived from swiss mice; immuno-competent; useful as control when studying immune defects in NOD/LtJ mice.

NOD/LTJ MHC CONGENICS

STRAIN NAME: NOD.B10-H2^b
STOCK NO.: 002591
MHC HAPLOTYPE: H2^b (K^b, A^b, E^null, D^b)
CHARACTERISTICS AND USES: Diabetes resistant MHC; exhibit some immune dysfunctions of NOD mice; useful in dissecting the role of MHC vs. non-MHC genes in producing immunological abnormalities.

STRAIN NAME: NOD.NON-H2^nb1
STOCK NO.: 001626
MHC HAPLOTYPE: H2^nb1 (K^b, A^nb1, E^k, D^b)
CHARACTERISTICS AND USES: Diabetes resistant MHC; exhibit some in dissecting the role of MHC vs. non-MHCimmune dysfunctions of NOD/LtJ mice; useful genes in producing immunological abnormalities.

STRAIN NAME: NON.NOD-H2^g7
STOCK NO.: 001627
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Diabetogenic MHC; exhibit some immune dysfunctions of NOD mice; useful in dissecting the role of MHC vs. non-MHC genes in producing immunological abnormalities.

STRAIN NAME: NOD.SWR-H2^q
STOCK NO.: 002032
MHC HAPLOTYPE: H2^q (K^q, A^q, E^q, D^q)
CHARACTERISTICS AND USES: Diabetes-resistant MHC; exhibit some immune dysfunctions of NOD mice; useful in dissecting the role of MHC vs. non-MHC genes in producing immunological abnormalities.

STRAIN NAME: B6.NOD-H2^g7
STOCK NO.: 003300
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Diabetogenic MHC on diabetes resistance background; useful in dissecting the role of MHC vs. non MHC genes in producing immunological abnormalities.

NOD/LtJ NON-MHC CONGENICS

STRAIN NAME: NOD.NON-Thy1^a/J
STOCK NO.: 002721
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Carries Thy1^a (THY1.1) T cell marker while NOD/LtJ mice are Thy1^b (THY1.2); useful in adoptive transfer of diabetes.

STRAIN NAME: NOD.NOR-Il1 (64-94cm)
STOCK NO.: 002346
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Congenic for interleukin 1 gene on Chr 2; useful for dissecting the role of non-MHC susceptibility genes in autoimmune diabetes.

NOD CONGENICS WITH MUTATIONS AFFECTING IMMUNOCOMPETENCE

STRAIN NAME: NOD/Lt-B2m^tm1Unc
STOCK NO.: 002309
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: MHC class I deficient; CD8 T cell deficient; diabetes resistant; excellent source for insulities-free, MHC class I-negative islets for transplantation studies.

STRAIN NAME: NOD/LtSz-Prkdc^scid/J
STOCK NO.: 001303
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: B & T cell deficient; C-5 deficient (Hc⁰); low NK cells; insulitis and diabetes free; high incidence of thymomas later in life; useful as source for insulitis-free islets, and for delineating the role of T cell subsets in causing diabetes in adoptive transfer studies.

STRAIN NAME: NOD/LtSz-Prkdc^scid Emv30^b
STOCK NO.: 002313
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: B & T cell deficient; C-5 deficient (Hc⁰); low NK cells; Emv30 null; retarded development of thymomas; insulitis and diabetes free; useful as source for insulitis-free islets, and for delineating the role of T cell subsets in causing diabetes in adoptive transfer studies.

STRAIN NAME: NOD/LtSz-Prkdc^scid B2m^tm1Unc
STOCK NO.: 003449
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null,  D^b<supb< sup="">)
CHARACTERISTICS AND USES: B & T cell deficient; C-5 deficient (Hc⁰); low NK cells; class I deficient; excellent source for insulitis free, MHC class I-negative islets for transplantation studies.

STRAIN NAME: NOD-Ifng^tm1
STOCK NO.: 002575
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: Interferon gamma deficient; useful for examining the role of interferon in autoimmune diabetes.

NOD TRANSGENICS

STRAIN NAME: NOD/Lt-Igh-6^tm1Cgn
STOCK NO.: 002572
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^null, D^b)
CHARACTERISTICS AND USES: B cell deficient; useful for studying the role of Beta lymphocytes in autoimmune diabetes.

STRAIN NAME: NOD/Lt-Tg(I-Ealpha,line 5)2Lt
STOCK NO.: 002034
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^Tg, D^b)
CHARACTERISTICS AND USES: Overexpress H2-E molecules on APCs; convey almost complete diabetes resistance; exhibit some immune dysfunctions of NOD mice; useful for the analysis of T cell repertoire development and presentation of Beta cell antigens.

STRAIN NAME: NOD/Lt-Tg(I-Ealpha,line 12)3Lt
STOCK NO.: 002035
MHC HAPLOTYPE: H2^g7 (K^d, A^g7, E^Tg, D^b)
CHARACTERISTICS AND USES: Overexpress H2-E molecules on APCs; convey partial diabetes resistance; exhibit diabetes; exhibit some immune dysfunctions of NOD mice; useful for the analysis of T cell repertoire development and presentation of Beta cell antigens.

This information was extracted from several information sources including the references listed below.

References

Authors in bold indicate Jackson Laboratory scientists

• Leiter EH, Atkinson MA (editors). 1998. The NOD Mice and Related Strains: Research Applications in Diabetes, AIDS, Cancer and Other Diseases. RG Landes, Austin 208 p.

• Leiter EH. 1997. The NOD mouse: a model for insulin-dependent diabetes mellitis. Current Protocols in Immunology 24 (Suppl):15.9.1-15.9.23.