Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation.
"Humanized" mouse models created by engraftment of immunodeficient mice with human hematolymphoid cells or tissues are an emerging technology with broad appeal across multiple biomedical disciplines. However, investigators wishing to utilize humanized mice with engrafted functional human immune systems are faced with a myriad of variables to consider. In this study, we analyze HSC engraftment methodologies using three immunodeficient mouse strains harboring the IL2rgamma(null) mutation; NOD-scid IL2rgamma(null), NOD-Rag1(null) IL2rgamma(null), and BALB/c-Rag1(null) IL2rgamma(null) mice. Strategies compared engraftment of human HSC derived from umbilical cord blood following intravenous injection into adult mice and intracardiac and intrahepatic injection into newborn mice. We observed that newborn recipients exhibited enhanced engraftment as compared to adult recipients. Irrespective of the protocol or age of recipient, both immunodeficient NOD strains support enhanced hematopoietic cell engraftment as compared to the BALB/c strain. Our data define key parameters for establishing humanized mouse models to study human immunity.
Brehm
Michael A
MA
Diabetes Division, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. michael.brehm@umassmed.edu
Cuthbert
Amy
A
Yang
Chaoxing
C
Miller
David M
DM
DiIorio
Philip
P
Laning
Joseph
J
Burzenski
Lisa
L
Gott
Bruce
B
Foreman
Oded
O
Kavirayani
Anoop
A
Herlihy
Mary
M
Rossini
Aldo A
AA
Shultz
Leonard D
LD
Greiner
Dale L
DL
D000818:Animals; D000831:Animals, Newborn; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006651:Histocytochemistry; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric
C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit