eNews April 01, 1999

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 H2g7 MHC haplotype (Kd, Ag7, Enull, Db).

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:
H2gx (Kd, Ag7, Enull, Dx)
CHARACTERISTICS AND USES: Alloxan-induced diabetes-resistance; closely related to NOD; MHC very similar to NOD (unique H2-Dx variant); useful as a closely related insulitis and diabetes free.

STRAIN NAME: ALS/LtJ
STOCK NO.:
003072
MHC HAPLOTYPE:
H2nb1 (Kd, Anb1, Ek, Db)
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: H2nb1 (Kb, Anb1, Ek, Db)
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:
H2g7 (Kd, Ag7, Enull, Db)
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:
H2s (Ks, As, Es, Ds)
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:
H2q (Kq, Aq, Eq, Dq)
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-H2b
STOCK NO.:
002591
MHC HAPLOTYPE:
H2b (Kb, Ab, Enull, Db)
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-H2nb1
STOCK NO.: 001626
MHC HAPLOTYPE:
H2nb1 (Kb, Anb1, Ek, Db)
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-H2g7
STOCK NO.:
001627
MHC HAPLOTYPE:
H2g7 (Kd, Ag7, Enull, Db)
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-H2q
STOCK NO.: 002032
MHC HAPLOTYPE:
H2q (Kq, Aq, Eq, Dq)
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-H2g7
STOCK NO.: 003300
MHC HAPLOTYPE:
H2g7 (Kd, Ag7, Enull, Db)
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-Thy1a/J
STOCK NO.: 002721
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
CHARACTERISTICS AND USES:
Carries Thy1a (THY1.1) T cell marker while NOD/LtJ mice are Thy1b (THY1.2); useful in adoptive transfer of diabetes.

STRAIN NAME: NOD.NOR-Il1 (64-94cm)
STOCK NO.:
002346
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
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-B2mtm1Unc
STOCK NO.:
002309
MHC HAPLOTYPE:
H2g7 (Kd, Ag7, Enull, Db)
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-Prkdcscid/J
STOCK NO.:
001303
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
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-Prkdcscid Emv30b
STOCK NO.:
002313
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
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-Prkdcscid B2mtm1Unc
STOCK NO.: 
003449
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull,  Db<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-Ifngtm1
STOCK NO.:
002575
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
CHARACTERISTICS AND USES: Interferon gamma deficient; useful for examining the role of interferon in autoimmune diabetes.

NOD TRANSGENICS

STRAIN NAME: NOD/Lt-Igh-6tm1Cgn
STOCK NO.:
002572
MHC HAPLOTYPE: H2g7 (Kd, Ag7, Enull, Db)
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:
H2g7 (Kd, Ag7, ETg, Db)
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: H2g7 (Kd, Ag7, ETg, Db)
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.