Rat Models of Human Type 1 Diabetes.

  title={Rat Models of Human Type 1 Diabetes.},
  author={Sigurd Lenzen and Tanja Arndt and Matthias Elsner and Dirk Wedekind and Anne J{\"o}rns},
  journal={Methods in molecular biology},
Rat models of human type 1 diabetes have been shown to be of great importance for the elucidation of the mechanisms underlying the development of autoimmune diabetes. The three major well-established spontaneous rat models are the BioBreeding (BB) diabetes-prone rat, the Komeda diabetes-prone (KDP) rat, and the IDDM (LEW.1AR1-iddm) rat. Their distinctive features are described with special reference to their pathology, immunology, and genetics and compared with the situation in patients with… 
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Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
The up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given.
Remission of autoimmune diabetes by anti-TCR combination therapies with anti-IL-17A or/and anti-IL-6 in the IDDM rat model of type 1 diabetes
Two therapies were initiated immediately after disease manifestation to reverse the diabetic metabolic state in the LEW resulting in sustained normoglycaemia with normalized serum C-peptide concentrations and the triple combination therapy achieved both goals in a complimentary anti-autoimmune and anti-inflammatory action.
Translation of curative therapy concepts with T cell and cytokine antibody combinations for type 1 diabetes reversal in the IDDM rat
The double antibody combination of anti-TCR with anti-TNF-α proved to be the most suited therapy for reversal of the T1D metabolic state due to effective beta cell regeneration in an infiltration free pancreas.


Rat models of type 1 diabetes: genetics, environment, and autoimmunity.
Data generated in the rat have correctly predicted the outcome of several human diabetes prevention trials, notably the failure of nicotinamide and low dose parenteral and oral insulin therapies.
Cblb is a major susceptibility gene for rat type 1 diabetes mellitus
The positional cloning of Iddm/kdp1 is reported and a nonsense mutation in Cblb is identified, a member of the Cbl/Sli family of ubiquitin-protein ligases, which functions as a negative regulator of autoimmunity and C Blb is a major susceptibility gene for type 1 diabetes in the rat.
Genetic Reconstitution of Autoimmune Type 1 Diabetes With Two Major Susceptibility Genes in the Rat
Despite the low incidence and delayed onset of diabetes, the congenic strain established in this study did develop the disease, indicating that type 1 diabetes can be reconstituted on a non-KDP genetic background with the RT1u haplotype and Cblb mutation.
Animal models of human type 1 diabetes for evaluating combination therapies and successful translation to the patient with type 1 diabetes
  • S. Lenzen
  • Medicine, Biology
    Diabetes/metabolism research and reviews
  • 2017
The advantages and disadvantages of the three spontaneous rat models as well as the NOD mouse, compared with the characteristics of human type 1 diabetes, are considered in this review.
Identification of a major gene responsible for type 1 diabetes in the Komeda diabetes-prone rat.
  • N. Yokoi
  • Biology, Medicine
    Experimental animals
  • 2005
A two-gene model of the development of type 1 diabetes in which two major susceptibility genes, Cblb and MHC, determine autoimmune reaction and tissue specificity to pancreatic beta-cells, respectively is proposed.
Induction of type I diabetes by Kilham's rat virus in diabetes-resistant BB/Wor rats.
A virus that was identified serologically as Kilham's rat virus (KRV) was isolated from a spontaneously diabetic rat and reproducibly induced diabetes in naive diabetes-resistant (DR) BB/Wor rats and may provide insight regarding the interaction of viruses and autoimmune disease.
Type 1 Diabetes in the BB Rat: A Polygenic Disease
This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes.
Lymphopenia in the BB rat model of type 1 diabetes is due to a mutation in a novel immune-associated nucleotide (Ian)-related gene.
It is shown that lymphopenia is due to a frameshift deletion in a novel member (Ian5) of the Immune-Associated Nucleotide (IAN)-related gene family, resulting in truncation of a significant portion of the protein.
BB rat lyp mutation and Type 1 diabetes
The consequences of the BB rat lyp mutation on T‐cell homeostasis, repertoire and function, as well as its role in the pathogenesis of type I diabetes are described.
LEW.1WR1 rats develop autoimmune diabetes spontaneously and in response to environmental perturbation.
A new rat model of autoimmune diabetes that arose in a major histocompatibility complex congenic LEW rat provides a new model for studying autoimmune diabetes and arthritis in an animal with a genetic predisposition to both disorders that can be amplified by environmental perturbation.