Strain Name: |
NOD/ShiLtJ-Leprdb-5J/LtJ |
|---|---|
Stock Number: |
004939 |
Availability: | Repository-Cryopreserved |
Price and Supply Information | |
General Terms and Conditions |
| Former Name |
NOD-Leprdb-5J/Lt (Changed: 07-MAR-07
) |
| Genes & Alleles | Lepr; Leprdb-5J; |
Product Information
Strain Details
Type JAX® GEMM® Strain - Coisogenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Species laboratory mouse Donating Investigator Edward Leiter, The Jackson Laboratory H2 Haplotype g7 Generation F105+4pN1 Appearance
albino
Related Genotype: A/A Tyrc/TyrcStrain Description
Co-isogenic, NOD/ShiLtJ- Leprdb-5J/LtJ (NOD- Leprdb-5J) homozygous mice develop juvenile onset obesity and type II diabetes coupled with suppression of spontaneous type I diabetes in which the NOD/ShiLtJ (NOD/Lt) strain is known. RT-PCR confirms the expression of the leptin receptor long isoform (Rb) in the hypothalamus. NOD/Lt mice homozygous for this mutation are viable and retain some fertility although the stock is maintained by heterozygous matings. By 5 weeks of age, homozygous mice are hyperphagic, eating twice the amount of mouse chow as lean controls and develop hyperglycemia not requiring insulin therapy for long tem survival (39+ weeks of age). Lean littermate mice (wildtype or heterozygotes) develop spontaneous type 1 diabetes in an age dependent (post-adolescent) manner. In contrast, Leprdb-5J homozygotes of both sexes develop hyperglycemia within 1-2 weeks of weaning. This is a type II diabetes based upon chronically elevated insulin and leptin levels maintained over periods up to 1 year. Pancreatic histopathology in most individuals shows islet hypertrophy with beta cell hyperplasia that is not restricted by insulitis. Insulitis, when present, is primarily peri-vascular/periductular and not intra-islet. Approximately 1/3 of mutants progress to an end-stage Type II diabetes with decreases in body weight and plasma insulin whereas 2/3 maintain obese body weight (35-45g) in association with a beta cell hypertrophy/hyperplasia phenotype (Lee et al., 2005). Originally, mutant males were reported as more severely affected than females, but current unpublished results show the same multiplicity of phenotypes in females. Serum lipid levels were not significantly increased in any of the Leprdb-5J homozygous mutant mice, current studies are showing an unexplained variability in this phenotype. No significant pathology was originally observed in the liver or kidney (Lee et al., 2005). Splenic leukocytes from young, hyperglycemic mutants transferred into NOD.Rag1 recipients did not transfer type I diabetes over 13 weeks; whereas wild-type donor cells did. However, widespread insulitis was transferred by Leprdb-5J donors, indicating that their splenocytes contained a less-activated effector population at the time of transfer. Reciprocal bone marrow transfers confirmed that Leprdb-5J marrow contained diabetogenic stem cells; however, the slower diabetes generated by either wildtype or mutant marrow transferred into irradiated Leprdb-5J recipients indicated that the disturbed metabolic milieu produced by the obesity mutation was the major reason for suppressing the diabetogenic potential of marrow precursors (Lee et al., 2006). Leptin has been reported to accelerate T1D onset in juvenile NOD females (Matarese et al., 2002). The leptin-resistant NOD- Leprdb-5J mouse is useful for dissecting the interaction between the endocrine and immune system in type 1 diabetes-prone mice; understanding the trophic factors generated to produce robust proliferation of B-cells; and studying the involvement of leptin signaling in cueing the cytopathic function of autoimmune T-effector cells.Strain Development
The recessive Leprdb-5J mutation in the leptin receptor gene (Chr. 4) arose spontaneously in the NOD/ShiLtJ (Stock No. 1976) production colony at The Jackson Laboratory in 2003 (Lee et al., 2005). The mutation was eliminated from breeder stock in the production colony but Dr. Edward Leiter retained heterozygous breeders. The Leprdb-5J mutation present in this NOD/Lt strain contains a G-T transversion mutation at position 640 encoding a valine instead of a glycine; eliminates a Hae III restriction site present in the wild-type receptor and resides in the distal portion of the extra-cellular domain (Lee et al., 2005). Thus, unlike the commonly studied Leprdb-1J mutation that lacks the intracellular signaling domain, the Leprdb-5J molecule retains an intact intracellular domain. In 2006, the T1DR received this strain at generation F105+4.
Mammalian Phenotype Terms assigned by genotype |
Gene & Allele Details
| Allele Symbol | Leprdb-5J | ||
|---|---|---|---|
| Allele Name | diabetes 5 Jackson | ||
| Mutation Made By | Edward Leiter, The Jackson Laboratory | ||
| Strain of Origin | NOD/ShiLtJ | ||
| Gene Symbol and Name | Lepr, leptin receptor | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | CD295; LEPROT; Leprb; Modb1; OB-RGRP; OBR; db; diabetes; leptin receptor gene-related protein; obese-like; obl; | ||
| Molecular Note | A G to T transversion mutation was found in exon 13 effecting a glycine640valine change in the receptor. [MGI Ref ID J:87061] | ||
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 001976 NOD/ShiLtJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for JAX® GEMM® Strains | ||
Genotyping Protocols
Leprdb-5J
Colony Maintenance
| Breeding & Husbandry | Homozygotes of both sexes breed. However, homozygote x homozygote crosses are often unproductive. |
|---|
Related Strains
NOD Strains
001976 NOD/ShiLtJ View NOD Strains (1 strain)
000709 129P3/J-Leprdb-3J/J 002048 B6 x C57BLKS-m Leprdb Myo15sh2-J/J 000697 B6.Cg-m +/+ Leprdb/J 000699 B6.Cg-m Leprdb/+ +/J 000642 BKS.Cg-m +/+ Leprdb/J 000700 BKS.Cg-m Leprdb/+ +/J 001192 BKS.Cg-meaJ Leprdb +/+ + m/J 000707 CBA.Cg-m Leprdb/+ +/J 006654 FVB.BKS(D)-Leprdb/ChuaJ 006846 STOCK Leprdb-9J/Jgn
Research Applications
This mouse can be used to support research in many areas including:
Leprdb-5J relatedDiabetes and Obesity Research
Hyperglycemia
Hyperinsulinemia
Diabetes and Obesity Research
Hyperglycemia
Hyperinsulinemia
References
Selected Reference(s)
Lee CH; Chen YG; Chen J; Reifsnyder PC; Serreze DV; Clare-Salzler M; Rodriguez M; Wasserfall C; Atkinson MA; Leiter EH. 2006. Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: II. Immunologic analysis. Diabetes 55(1):171-8. [PubMed: 16380490] [MGI Ref ID J:118304]
Lee CH; Reifsnyder PC; Naggert JK; Wasserfall C; Atkinson MA; Chen J; Leiter EH. 2005. Novel leptin receptor mutation in NOD/LtJ mice suppresses type 1 diabetes progression: I. Pathophysiological analysis. Diabetes 54(9):2525-32. [PubMed: 16123339] [MGI Ref ID J:118305]
Leiter EH; Lee C-H; Reifsnyder PC; Naggert JK. 2004. Leptin receptor deficiency in NOD/LtJ mice produces a type 2 diadetes syndrome with suppressed autoimmunity MGI Direct Data Submission :. [MGI Ref ID J:87061]
Price and Supply Information
| Strain Name: | NOD/ShiLtJ-Leprdb-5J/LtJ |
| Stock Number: | 004939 |
Price Details
IMPORTANT NOTE: Prices are based on shipping destination. The shipping destinations are:
- USA, Canada and Mexico
- International
*Pricing for Shipping Destination selected:
USA, Canada and Mexico
| Price(s) in US dollars ($) | |||||
|---|---|---|---|---|---|
| Cryorecovery Fee | $1900.00 | ||||
Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. |
| Licensing | See General Terms and Conditions below |
| Control Information | View Control Information in Strain Details. View Control Pricing Information for JAX® Strains. |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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