Bridging mice to men: Using HLA transgenic mice to enhance the future prediction and prevention of autoimmune type 1 diabetes in humans

David V. Serreze, Marijke Niens, John Kulik, Teresa P. DiLorenzo

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Citations (Scopus)

Abstract

Similar to the vast majority of cases in humans, the development of type 1 diabetes (T1D) in the NOD mouse model is due to T-cell mediated autoimmune destruction of insulin-producing pancreatic β cells. Particular major histocompatibility complex (MHC) haplotypes (designated HLA in humans and H2 in mice) provide the primary genetic risk factor for T1D development. It has long been appreciated that within the MHC, particular unusual class II genes contribute to the development of T1D in both humans and NOD mice by allowing for the development and functional activation of β-cell autoreactive CD4 T cells. However, studies in NOD mice have revealed that through interactions with other background susceptibility genes, the quite common class I variants (K d, D b) characterizing this strain's H2 g7 MHC haplotype aberrantly acquire an ability to support the development of β cell autoreactive CD8 T-cell responses also essential to T1D development. Similarly, recent studies indicate that in the proper genetic context some quite common HLA class I variants also aberrantly contribute to T1D development in humans. This chapter will focus on how "humanized" HLA transgenic NOD mice can be created and used to identify class I-dependent β cell autoreactive CD8 T-cell populations of clinical relevance to T1D development. There is also discussion on how HLA transgenic NOD mice can be used to develop protocols that may ultimately be useful for the prevention of T1D in humans by attenuating autoreactive CD8 T-cell responses against pancreatic β cells.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
Pages119-134
Number of pages16
Volume602
DOIs
StatePublished - 2010

Publication series

NameMethods in Molecular Biology
Volume602
ISSN (Print)10643745

Fingerprint

Type 1 Diabetes Mellitus
Transgenic Mice
Inbred NOD Mouse
T-Lymphocytes
Major Histocompatibility Complex
Human Development
Haplotypes
MHC Class II Genes
Aptitude
Insulin
Population
Genes

Keywords

  • "humanized" NOD mice
  • autoimmunity
  • HLA transgenics
  • T cells
  • Type 1 diabetes (T1D)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Medicine(all)

Cite this

Serreze, D. V., Niens, M., Kulik, J., & DiLorenzo, T. P. (2010). Bridging mice to men: Using HLA transgenic mice to enhance the future prediction and prevention of autoimmune type 1 diabetes in humans. In Methods in Molecular Biology (Vol. 602, pp. 119-134). (Methods in Molecular Biology; Vol. 602). https://doi.org/10.1007/978-1-60761-058-8_8

Bridging mice to men : Using HLA transgenic mice to enhance the future prediction and prevention of autoimmune type 1 diabetes in humans. / Serreze, David V.; Niens, Marijke; Kulik, John; DiLorenzo, Teresa P.

Methods in Molecular Biology. Vol. 602 2010. p. 119-134 (Methods in Molecular Biology; Vol. 602).

Research output: Chapter in Book/Report/Conference proceedingChapter

Serreze, DV, Niens, M, Kulik, J & DiLorenzo, TP 2010, Bridging mice to men: Using HLA transgenic mice to enhance the future prediction and prevention of autoimmune type 1 diabetes in humans. in Methods in Molecular Biology. vol. 602, Methods in Molecular Biology, vol. 602, pp. 119-134. https://doi.org/10.1007/978-1-60761-058-8_8
Serreze, David V. ; Niens, Marijke ; Kulik, John ; DiLorenzo, Teresa P. / Bridging mice to men : Using HLA transgenic mice to enhance the future prediction and prevention of autoimmune type 1 diabetes in humans. Methods in Molecular Biology. Vol. 602 2010. pp. 119-134 (Methods in Molecular Biology).
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