This strain is a polygenic model for type 1 diabetes. Diabetes in NOD/ShiLtJ mice is characterized by insulitis, a leukocytic infiltration of the pancreatic islets. Marked decreases in pancreatic insulin content occur in females at about 12 weeks of age and several weeks later in males. Consequently, plasma glucose levels increase to greater than 250mg/dl.
This strain is homozygous for Cdh23ahl, the age related hearing loss 1 mutation, which on this background results in progressive hearing loss that is already severe by three months of age.
Diabetes in NOD/ShiLtJ mice is characterized by insulitis, a leukocytic infiltrate of the pancreatic islets. Marked decreases in pancreatic insulin content occur in females at about 12 weeks of age and several weeks later in males. Onset of diabetes is marked by moderate glycosuria and by a non-fasting plasma glucose higher than 250 mg/dl. Diabetic mice are hypoinsulinemic and hyperglucagonemic, indicating a selective destruction of pancreatic islet beta cells. Susceptibility to IDDM in NOD/ShiLtJ mice is polygenic, and environment, including housing conditions, health status, and diet, exerts a strong effect on penetrance. NOD/ShiLtJ females are more widely used than males because the onset of IDDM symptoms occurs earlier and with a higher incidence (90-100% by 30 weeks of age). NOD/ShiLtJ males develop IDDM at a frequency of between 40-60% by 30-40 weeks of age. Male mice are useful for certain applications, including pharmaceutical studies, "accelerated transfer" of IDDM, and some in vitro studies. The major component of diabetes susceptibility in NOD mice is the unique MHC haplotype (H2g7 = Kd, Aad, Abg7, Enull, Db). NOD mice also exhibit multiple aberrant immunophenotypes including defective antigen presenting cell immunoregulatory functions, defects in the regulation of theT lymphocyte repertoire, defective NK cell function, defective cytokine production from macrophages (Fan et al., 2004) and impaired wound healing. They also lack hemolytic complement, C5. NOD/ShiLtJ mice also are severely hearing-impaired. A variety of mutations causing immunodeficiencies, targeted mutations in cytokine genes, as well as transgenes affecting immune functions, have been backcrossed into the NOD/ShiLt inbred strain background.
NOD inbred mice originated early on in the inbreeding of the Cataract Shionogi (CTS) strain. These mice were originally outbred Jcl:ICR mice. At F6, the progenitors of the future NOD/Shi mice were inbred on the basis of an elevated fasting blood glucose level in cataract-free mice. At F13, the NOD progenitors were separated from what is now the NON/Shi strain. High fasting blood glucose levels continued to be the basis for selection of the latter strain, while the NOD progenitors at F13 and later were selected on the basis of a normal fasting blood glucose level. In 1974, at F20, a female in the "normoglycemic" line spontaneously developed overt insulin-dependent diabetes mellitus with insulitis (IDDM). Selective breeding of the progeny of this diabetic female produced the nonobese diabetic (NOD) strain. Originally restricted to distribution in Japan, NOD substrains were distributed during the early 1980s to Australia and the United States. NOD and NON strains were imported from a colony in Kyoto, Japan by Dr. M. Hattori to the Joslin Diabetes Ceneter in Boston in 1984. Breeder pairs from this importation were sent from The Joslin Diabetes Center to Dr. E Leiter at The Jackson Laboratory, and are the source of the production strains NOD/ShiLtJ and NON/ShiLtJ. The current generation of inbreeding is F83.
|Allele Name||age related hearing loss 1|
|Allele Synonym(s)||Cdh23753A; mdfw|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|Gene Synonym(s)||4930542A03Rik; 4930542A03Rik; CDHR23; RIKEN cDNA 4930542A03 gene; USH1D; W; age related hearing loss 1; ahl; ahl; bob; bob; bobby; bus; bustling; mdfw; mdfw; modifier of deaf waddler; neuroscience mutagenesis facility, 112; neuroscience mutagenesis facility, 181; neuroscience mutagenesis facility, 252; nmf112; nmf112; nmf181; nmf181; nmf252; nmf252; sals; sals; salsa; v; waltzer|
|Strain of Origin||multiple strains|
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