scholarly journals Use of recombinant congenic and congenic strains of NOD mice to identify a new insulin-dependent diabetes resistance gene.

1994 ◽  
Vol 180 (4) ◽  
pp. 1553-1558 ◽  
Author(s):  
D V Serreze ◽  
M Prochazka ◽  
P C Reifsnyder ◽  
M M Bridgett ◽  
E H Leiter
Keyword(s):  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Resistance Locus ◽  
Mhc Genes ◽  
Histocompatibility Complex ◽  
Insulin Dependent ◽  
Recombinant Congenic Strain ◽  
Mhc Haplotype

Insulin-dependent diabetes mellitus (IDDM) in NOD/Lt mice represents a complex polygenic disease. NOR/Lt is a recombinant congenic strain (RCS) in which limited regions of the NOD/Lt genome have been replaced by genome from the C57BL/KsJ strain. NOR mice are insulitis resistant and diabetes free despite genetic identity with NOD at numerous chromosomal regions containing previously described insulin-dependent diabetes (Idd) genes, including the strongly diabetogenic H2g7 major histocompatibility complex (MHC) haplotype. The present study revealed BKs-derived genome on segments of chromosomes (Chr) 1, 2, 4, 5, 7, 11, 12, and 18, approximating 11.6% of the total NOR genome analyzed. (NOD x NOR)F2 segregation analysis was employed to identify chromosomal regions in NOR containing Idd resistance alleles. IDDM developed in 33% (10/30) of F1 females, and 29.3% (36/123) of F2 females aged to 1 yr. A previously unrecognized diabetes resistance locus (designated Idd13r) strongly protective in homozygous state was identified on NOR Chr 2 in linkage with the Il1 alpha structural gene. The existence of this locus was confirmed by construction of a NOD stock congenic for NOR-derived markers on Chr 2. Our analysis shows the utility of RCS and congenic stocks for the identification and isolation of non-MHC genes with strong antidiabetogenic functions.

scholarly journals Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence.

1990 ◽  
Vol 171 (6) ◽  
pp. 2077-2089 ◽  
Author(s):  
M B Oldstone
Keyword(s):  
Diabetes Mellitus ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Insulin Dependent Diabetes Mellitus ◽  
Lymphocytic Infiltration ◽  
Lymphocytic Choriomeningitis ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Beta Cell Destruction ◽  
Insulin Dependent

A situation in which virus can be used as a therapeutic agent to prevent a lethal autoimmune disease is explored. Nonobese insulin-dependent diabetes (NOD) mice spontaneously develop insulin-dependent diabetes mellitus (IDDM), characterized by lymphocytic infiltration into the islets of Langerhans and beta cell destruction, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. Infection of NOD mice with lymphocytic choriomeningitis virus (LCMV) aborts the autoimmune manifestations and resultant IDDM. The viruses' effect is on a subset of CD4+ lymphocytes. Ablating this autoimmune diabetes does not significantly alter immune responses to a variety of non-LCMV antigens that require CD4+ lymphocyte participation. The prevention of IDDM associated with viral therapy is maintained throughout the life spans of NOD mice.

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