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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, Michael Brehm, Amy Cuthbert, Chaoxing Yang, David Miller, Philip Diiorio, Joseph Laning, Lisa Burzenski, Bruce Gott, Oded Foreman, Anoop Kavirayani, Mary Herlihy, Aldo Rossini, Leonard Shultz, Dale Greiner Mar 2012

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, Michael Brehm, Amy Cuthbert, Chaoxing Yang, David Miller, Philip Diiorio, Joseph Laning, Lisa Burzenski, Bruce Gott, Oded Foreman, Anoop Kavirayani, Mary Herlihy, Aldo Rossini, Leonard Shultz, Dale Greiner

Philip J diIorio Jr

"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 …


Human Immune System Development And Rejection Of Human Islet Allografts In Spontaneously Diabetic Nod-Rag1null Il2rgammanull Ins2akita Mice, Michael Brehm, Rita Bortell, Philip Diiorio, Jean Leif, Joseph Laning, Amy Cuthbert, Chaoxing Yang, Mary Herlihy, Lisa Burzenski, Bruce Gott, Oded Foreman, Alvin Powers, Dale Greiner, Leonard Shultz Mar 2012

Human Immune System Development And Rejection Of Human Islet Allografts In Spontaneously Diabetic Nod-Rag1null Il2rgammanull Ins2akita Mice, Michael Brehm, Rita Bortell, Philip Diiorio, Jean Leif, Joseph Laning, Amy Cuthbert, Chaoxing Yang, Mary Herlihy, Lisa Burzenski, Bruce Gott, Oded Foreman, Alvin Powers, Dale Greiner, Leonard Shultz

Philip J diIorio Jr

OBJECTIVE: To create an immunodeficient mouse model that spontaneously develops hyperglycemia to serve as a diabetic host for human islets and stem cell-derived beta-cells in the absence or presence of a functional human immune system.

RESEARCH DESIGN AND METHODS: We backcrossed the Ins2(Akita) mutation onto the NOD-Rag1(null) IL2rgamma(null) strain and determined 1) the spontaneous development of hyperglycemia, 2) the ability of human islets, mouse islets, and dissociated mouse islet cells to restore euglycemia, 3) the generation of a human immune system following engraftment of human hematopoietic stem cells, and 4) the ability of the humanized mice to reject human islet …