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Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease.
Methods Mol Biol. 2010; 602:105-17.MM

Abstract

Immunodeficient mice have been used as recipients of human peripheral blood mononuclear cells (PBMC) for in vivo analyses of human xeno-graft-versus-host disease (GVHD). This xeno-GVHD model system in many ways mimics the human disease. The model system is established by intravenous or intraperitoneal injection of human PBMC or spleen cells into unconditioned or irradiated immunodeficient recipient mice. Recently, the development of several stocks of immunodeficient Prkdc (scid) (scid) and recombination activating 1 or 2 gene (Rag1 or Rag2) knockout mice bearing a targeted mutation in the gene encoding the IL2 receptor gamma chain (IL2rgamma) have been reported. The addition of the mutated IL2rgamma gene onto an immunodeficient mouse stock facilitates heightened engraftment with human PBMC. Stocks of mice with mutations in the IL2rgamma gene have been studied in several laboratories on NOD-scid, NOD-Rag1 (null), BALB/c-Rag1 (null), BALB/c-Rag2 (null), and Stock-H2(d)-Rag2 (null) strain backgrounds. Parameters to induce human xeno-GVHD in H2(d)-Rag2 (null) IL2rgamma (null) mice have been published, but variability in the frequency of disease and kinetics of GVHD were observed. The availability of the NOD-scid IL2rgamma (null) stock that engrafts more readily with human PBMC than does the Stock-H2(d)-Rag2 (null) IL2rgamma (null) stock should lead to a more reproducible humanized mouse model of GVHD and for the use in drug evaluation and validation. Furthermore, GVHD in human PBMC-engrafted scid mice has been postulated to result predominately from a human anti-mouse major histocompatibility complex (MHC) class II reactivity. Our recent development of NOD-scid IL2rgamma (null) beta2m (null) and NOD-scid IL2rgamma (null) Ab (null) stocks of mice now make it possible to investigate directly the role of host MHC class I and class II in the pathogenesis of GVHD in humanized mice using NOD-scid IL2rgamma (null) stocks that engraft at high levels with human PBMC and are deficient in murine MHC class I, class II, or both classes of MHC molecules.

Authors+Show Affiliations

Department of Medicine, The University of Massachusetts Medical School, Worcester, MA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20012395

Citation

Pino, Steve, et al. "Development of Novel Major Histocompatibility Complex Class I and Class II-deficient NOD-SCID IL2R Gamma Chain Knockout Mice for Modeling Human Xenogeneic Graft-versus-host Disease." Methods in Molecular Biology (Clifton, N.J.), vol. 602, 2010, pp. 105-17.
Pino S, Brehm MA, Covassin-Barberis L, et al. Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease. Methods Mol Biol. 2010;602:105-17.
Pino, S., Brehm, M. A., Covassin-Barberis, L., King, M., Gott, B., Chase, T. H., Wagner, J., Burzenski, L., Foreman, O., Greiner, D. L., & Shultz, L. D. (2010). Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease. Methods in Molecular Biology (Clifton, N.J.), 602, 105-17. https://doi.org/10.1007/978-1-60761-058-8_7
Pino S, et al. Development of Novel Major Histocompatibility Complex Class I and Class II-deficient NOD-SCID IL2R Gamma Chain Knockout Mice for Modeling Human Xenogeneic Graft-versus-host Disease. Methods Mol Biol. 2010;602:105-17. PubMed PMID: 20012395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of novel major histocompatibility complex class I and class II-deficient NOD-SCID IL2R gamma chain knockout mice for modeling human xenogeneic graft-versus-host disease. AU - Pino,Steve, AU - Brehm,Michael A, AU - Covassin-Barberis,Laurence, AU - King,Marie, AU - Gott,Bruce, AU - Chase,Thomas H, AU - Wagner,Jennifer, AU - Burzenski,Lisa, AU - Foreman,Oded, AU - Greiner,Dale L, AU - Shultz,Leonard D, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/2/23/medline SP - 105 EP - 17 JF - Methods in molecular biology (Clifton, N.J.) JO - Methods Mol. Biol. VL - 602 N2 - Immunodeficient mice have been used as recipients of human peripheral blood mononuclear cells (PBMC) for in vivo analyses of human xeno-graft-versus-host disease (GVHD). This xeno-GVHD model system in many ways mimics the human disease. The model system is established by intravenous or intraperitoneal injection of human PBMC or spleen cells into unconditioned or irradiated immunodeficient recipient mice. Recently, the development of several stocks of immunodeficient Prkdc (scid) (scid) and recombination activating 1 or 2 gene (Rag1 or Rag2) knockout mice bearing a targeted mutation in the gene encoding the IL2 receptor gamma chain (IL2rgamma) have been reported. The addition of the mutated IL2rgamma gene onto an immunodeficient mouse stock facilitates heightened engraftment with human PBMC. Stocks of mice with mutations in the IL2rgamma gene have been studied in several laboratories on NOD-scid, NOD-Rag1 (null), BALB/c-Rag1 (null), BALB/c-Rag2 (null), and Stock-H2(d)-Rag2 (null) strain backgrounds. Parameters to induce human xeno-GVHD in H2(d)-Rag2 (null) IL2rgamma (null) mice have been published, but variability in the frequency of disease and kinetics of GVHD were observed. The availability of the NOD-scid IL2rgamma (null) stock that engrafts more readily with human PBMC than does the Stock-H2(d)-Rag2 (null) IL2rgamma (null) stock should lead to a more reproducible humanized mouse model of GVHD and for the use in drug evaluation and validation. Furthermore, GVHD in human PBMC-engrafted scid mice has been postulated to result predominately from a human anti-mouse major histocompatibility complex (MHC) class II reactivity. Our recent development of NOD-scid IL2rgamma (null) beta2m (null) and NOD-scid IL2rgamma (null) Ab (null) stocks of mice now make it possible to investigate directly the role of host MHC class I and class II in the pathogenesis of GVHD in humanized mice using NOD-scid IL2rgamma (null) stocks that engraft at high levels with human PBMC and are deficient in murine MHC class I, class II, or both classes of MHC molecules. SN - 1940-6029 UR - https://www.unboundmedicine.com/medline/citation/20012395/Development_of_novel_major_histocompatibility_complex_class_I_and_class_II_deficient_NOD_SCID_IL2R_gamma_chain_knockout_mice_for_modeling_human_xenogeneic_graft_versus_host_disease_ L2 - https://dx.doi.org/10.1007/978-1-60761-058-8_7 DB - PRIME DP - Unbound Medicine ER -