Humanized NOD/LtSz-scid IL2 receptor common gamma chain knockout mice in diabetes research.
There are many rodent models of autoimmune diabetes that have been used to study the pathogenesis of human type 1 diabetes (T1D), including the non-obese diabetic (NOD) mouse, the biobreeding (BB) rat, and the transgenic mouse models. However, mice and rats are not humans, and these rodent models do not completely recapitulate the autoimmune pathogenesis of the human disease. In addition, many of the reagents, tools, and therapeutics proposed for use in humans may be species specific and cannot be investigated in rodents. Researchers have used nonhuman primates to more closely mimic the human immune system and, to study species-specific therapeutics, but these studies are associated with additional ethical and economic constraints and, to date, no model of autoimmune diabetes in this species has been described. New animal models are needed that will permit the in vivo investigation of human immune systems and analyses of the pathogenesis of human T1D without putting individuals at risk. To fill this need, we are developing humanized mouse models for the in vivo study of T1D. These models are based on our newly generated stock of NOD-scid IL2rgamma(null) mice, which engraft at higher levels with human hematolymphoid cells and exhibit enhanced function of the engrafted human immune systems compared with previous humanized mouse models. Overall, development of these new generations of humanized mice should facilitate in vivo studies of the human immune system as well as permit the investigation of the pathogenesis and effector phases of human T1D.
Shultz
Leonard D
LD
Division of Diabetes, Department of Medicine, 373 Plantation Street, Biotech 2, Suite 218, Worcester, MA 01605, USA.
Pearson
Todd
T
King
Marie
M
Giassi
Lisa
L
Carney
Lisa
L
Gott
Bruce
B
Lyons
Bonnie
B
Rossini
Aldo A
AA
Greiner
Dale L
DL
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D015203:Reproducibility of Results
D053631:Interleukin Receptor Common gamma Subunit