Type 1 Diabetes Resource Mission Expands

JAX® NOTES Issue 506, Summer 2006

Most cases of type 1 diabetes, or insulin dependent diabetes mellitus (IDDM), are characterized by an autoimmune destruction of the pancreatic beta cells. As a result, patients produce little or no insulin. Although treatments have improved, more effective methods of detecting, preventing, and treating this disease will depend on additional research, much of it in model organisms, especially the mouse. For example, the major cause of end-stage renal disease in type 1 diabetes patients is diabetic nephropathy, often preceded by hyperglycemia and hypertension. Few of the alleles associated with nephropathy risk in humans have been found. However, researchers are starting to discover them in the mouse, which should greatly facilitate identifying them in humans (Breyer et al. 2007, 2006). To accelerate the discovery of these and other diabetes-associated alleles, new mouse models, especially ones that develop diabetic complications, must be found or developed. The Type 1 Diabetes Resource (T1DR) has an expanded mission to help identify, produce, and distribute these new models to the research community.

Beginnings

In October, 2001, thanks to a five-year grant from the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), the Type 1 Diabetes Resource was established here at The Jackson Laboratory. It was administered through the National Center for Research Resources (NCRR) and co-directed by our scientists Drs. Muriel Davisson, Edward Leiter, and David Serreze. Initially, T1DR's mission was to import, rederive to full-barrier specific pathogen free (SPF) health status, cryopreserve, curate, and distribute 20-30 genetically-modified mouse models relevant to the study and treatment of type 1 diabetes and its complications per year. It also had a research component for generating or modifying specific models and for performing extensive genetic and phenotypic quality control. Primarily, its focus was to acquire genetically-modified stocks of the NOD strain, the premier animal model for studying type 1 diabetes. Since its inception, the T1DR has acquired approximately 150 such stocks (including transgenics, knockouts, and congenics) from both internal and external investigators. Among these is a large collection of congenics for chromosomal intervals with diabetes susceptibility or resistance loci, stocks with different major histocompatibility complex (MHC) regions, and "humanized" stocks expressing HLA alleles associated with increased diabetes risk.

The Expanded Mission

In February, 2007, the T1DR, through a contract with NIDDK, expanded its mission to serve as the Mouse Generation and Husbandry Core (MGHC) for the Animal Models of Diabetes Complications Consortium (AMDCC). The mission of the AMDCC is to coordinate efforts to produce and/or improve and characterize animal models of human diabetic complications, including diabetic kidney disease, vascular disease, retinopathy, neuropathy, and diabetic cardiomyopathy. To complement that mission, the T1DR will now produce, maintain, expand, phenotype, and distribute new strains established in cooperation with the AMDCC. Because available mouse models of both type 1 and type 2 diabetes are resistant to developing complications, the T1DR will aim to increase complication susceptibility by introducing 5-10 genetic manipulations per year into diabetes-developing strains. Additionally, staff at the Mouse Phenome Database will help determine which JAX® Mice strains are sensitized to diabetes complications.

Distributing T1DR Strains

Whenever possible, T1DR will continue to distribute functionally related groups of stocks live for a limited time. For example, a recently distributed group consisted primarily of various cytokine knockouts with an NOD background. Seven groups of 6-15 strains each have been distributed live since May 2005. If demand for a given stock continues past the live distribution window, the stock is maintained live until the demand is met.

If demand continues, the stock is transferred to the Induced Mutant Resource within our Repository for long-term availability. Investigators are offered either 3 breeding pairs or up to 6 single sex mice per strain. Currently, approximately 56 strains are available for live distribution (41 from external and 15 from internal donors).

If a strain is cryopreserved, JAX® Mice and Services can recover it at additional cost, or ship it as frozen embryos. Most investigators prefer receiving live mice. Over 140 of the nearly 160 TIDR strains are cryopreserved. (We offer an annual workshop on shipping and reconstituting cryopreserved embryos. See our Courses and Conferences Web site.

Submitting a Strain to the T1DR

You may donate type 1 diabetes and other models to our Repository by completing a strain submission form, available from the following Web site. By submitting a model to the Repository, you accrue several benefits, including the following:

  • you meet your obligations to share grant-generated resources;
  • you do not have to maintain mouse colonies no longer required for your research;
  • the Repository cryopreserves your stock, insuring it against catastrophic losses, such as those recently experienced at animal facilities in New Orleans;
  • the Repository performs extensive genetic quality control on all acquired strains and, in many instances, phenotypes them to verify published information;
  • the Repository more fully characterizes high demand strains; and
  • the Repository ensures that each strain receives proper nomenclature, is described and entered into the JAX® Mice Database, and that its availability to the scientific community is announced on our Web sites and in our print publications.

References

Breyer MD, Tchekneva E, Qi Z, Takahashi T, Fogo AB, Zhao HJ, Harris RC. 2007. Genetics of diabetic nephropathy: lessons from mice. Semin Nephrol 27:237-47.

Breyer MD, Qi Z, Tchekneva E. 2006. Diabetic nephropathy: leveraging mouse genetics. Curr Opin Nephrol Hypertens 15:227-32.