HUmanized Mice for Assays to Normalize Endocrine Pancreas Function
The scientific goal for the HUMANE CBP is to develop in vivo systems and assays to measure reconstitution of beta cell function. Developing qualitative and/or quantitative clonogenic in vivo assays able to assess the ability of transplanted beta stem or progenitor cells to reconstitute any pancreatice cell lineage in diabetic animals is the focus of the HUMANE CBP. To accomplish this, the HUMANE team is engineering beta-cell ablation models onto immunodeficient mouse strains to allow engraftment of strain-mismatched or species-mismatched stem/progenitors for beta cell reconstitution/clonogenic assays. The long term goal is to provide models for human beta stem and progenitor cells that will also support the development of a human immune system so that human beta cell function can be evaluated in the context of human immunity and autoimmunity.
Background
A schematic diagram of the development of various immunodeficient mouse models for the HUMANE project. Progress in the development of humanized mouse models was advanced by the discovery of the severe combined immunodeficiency (scid) gene mutation, which occurs spontaneously on the CB17 strain background. Another important advance came from crossing mice with the scid mutation onto the non-obese diabetic (NOD) strain, which led to improved engraftment of human haematopoietic cells owing to decreased natural killer (NK)-cell activity and decreased innate immunity. A breakthrough in the effectiveness of humanized mice came from crossing immunodeficient mice homozygous for targeted mutations at the interleukin-2 receptor (IL-2R) gamma-chain locus (Il2rg) onto the NOD-scid, NOD-Rag1-/- strain backgrounds. (Modified from Shultz et al (2007) Nature Rev. Immunol. 7, 118-130)
Attributions
The mouse illustration was obtained from the Open Clip Art Library and created by the user known as "Lemmling".
