These mice carry the retinal degeneration (Pde6b) mutation and exhibit certain tendencies toward autoimmune disease. A low plasma insulin level is characteristic. Immunologic abnormalities include perivascular/periductular leukocyte infiltration into the pancreas and submandibular salivary glands, and T lymphocytopenia in spleen. Both males and females show early impaired glucose tolerance, development of moderate mature-onset obesity in the presence of low plasma insulin levels, and development of glomerulosclerotic kidney lesions. This strain is useful as a model for type 2 (NIDDM) diabetes.Read More +
This strain is homozygous for the retinal degeneration allele Pde6brd1. See article "Genetic Background Effects: Can Your Mice See?", JAX® NOTES Spring 2002, No. 485.
Although closely related to NOD mice, NON mice contain a diabetes resistant MHC haplotype (H2nb1 = Kb, Anb1, Ek, Db). The name was derived from "Non-Obese Non-diabetic"; however, NON/ShiLtJ mice should not be considered "normal." They carry the retinal degeneration (Pde6b) mutation and exhibit certain tendencies toward autoimmune disease. This strain maintains a low plasma insulin level, which may account in part why certain loci from NON/ShiLt can enhance development of autoimmune type 1 diabetes in segregating hybrid mice following outcross to NOD/ShiLtJ. The NON strain-characteristic immunologic abnormalities include perivascular/periductular leukocyte infiltration into the pancreas and submandibular salivary glands, and T lymphocytopenia evident by 20 weeks of age in spleen. NON/ShiLt mice clearly harbor genes predisposing to type 2 diabetes, as evidenced by early impaired glucose tolerance in males and females, development of moderate mature-onset obesity in the presence of low plasma insulin levels, and development of glomerulosclerotic kidney lesions. The ALS/Lt strain shares the H2nb1 MHC haplotype with NON/ShiLt. Although ALS/Lt males share the impaired glucose tolerance phenotype of NON/ShiLt males, the ALS/Lt males differ in developing progressive hyperinsulinemia as they gain weight whereas NON/ShiLt males fail to hypersecrete insulin, suggesting a potential beta cell response defect in the latter strain. F1 hybrids of NON/ShiLt and NZO/Hl provide a new model of obesity-induced diabetes. Male (NON/ShiLt x NZO/Hl)F1 hybrids are obese (Body Weight = 53.5 g by 16 weeks) and almost all develop maturity onset NIDDM. F1 males on a 4% diet will develop hyperglycemia around 20 to 24 weeks of age; increasing the fat content of the diet accelerates diabetes onset to 16 to 20 weeks of age. (NZO/Hl x NON/ShiLt)F1 hybrids will develop diabetes slightly faster than their reciprocal cross due to the NZO maternal environment; however this cross is difficult to produce due to the inherently poor breeding performance of NZO/HlJ female mice. F1 females exhibit a weight gain similar to the NZO parent, and have impaired glucose tolerance but are resistant to diabetes development. Diabetes development can be accelerated to eight to 12 weeks by fostering onto an F1 dam. Reciprocal backcrosses to the parental strains and analysis of (NON/ShiLt x NZO/Hl)F2 mice has led to the identification of a number of complex diabetes-predisposing ("diabesity") QTLs. Dr. Leiter's research group at The Jackson Laboratory is currently developing a series of nine recombinant congenic strains (RCS) made by backcrossing the (NZO/Hl x NON/ShiLt)F1 for two generations onto the NON/ShiLt background before inbreeding (~12% NZO/Hl, 88% NON/ShiLt genomes). Preliminary analysis indicates that body weight gains of all RCS are higher than NON/ShiLt, but none are as obese as NZO/Hl; some of these RCS develop NIDDM while others are resistant. These new strains will be useful to further analyze diabesity QTLs and as new models for type 2 (NIDDM) diabetes. An additional benefit of the RCS is better breeding performance than NZO/Hl.
The NON inbred strain arose out of a colony originally developed by selection for high fasting blood glucose early in the inbreeding of the Cataract Shionogi (CTS) strain. These mice were originally outbred Jcl:ICR mice. A cataract-free substrain was initiated at F6, with selection made on the basis of a high fasting blood glucose. This line was separated from the future NOD/Shi line at F13, and originally designated NON for nonobese nondiabetic.
|Allele Name||retinal degeneration 1|
|Allele Synonym(s)||retinal degeneration 1; Pde6brd1|
|Gene Symbol and Name||Pde6b, phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide|
|Gene Synonym(s)||rd; rd1; Pdeb; r; rd; rd10; nmf137; r; retinal degeneration; retinal degeneration 1; retinal degeneration 10; CSNB3; CSNBAD2; rd1; rd-1; rd10; PDEB; RP40; phosphodiesterase, cGMP, rod receptor, beta polypeptide; Pdeb; GMP-PDEbeta|
|Strain of Origin||various|
|General Note||The following inbred strains are known to be homozygous for Pde6b |
|Molecular Note||Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C to A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain has also been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.|
When using the NON/ShiLtJ mouse strain in a publication, please include JAX stock #002423 in your Materials and Methods section.
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