title: NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells.
abstract: To establish a more appropriate animal recipient for xenotransplantation, NOD/SCID/gamma(c)(null) mice double homozygous for the severe combined immunodeficiency (SCID) mutation and interleukin-2Rgamma (IL-2Rgamma) allelic mutation (gamma(c)(null)) were generated by 8 backcross matings of C57BL/6J-gamma(c)(null) mice and NOD/Shi-scid mice. When human CD34+ cells from umbilical cord blood were transplanted into this strain, the engraftment rate in the peripheral circulation, spleen, and bone marrow were significantly higher than that in NOD/Shi-scid mice treated with anti-asialo GM1 antibody or in the beta2-microglobulin-deficient NOD/LtSz-scid (NOD/SCID/beta2m(null)) mice, which were as completely defective in NK cell activity as NOD/SCID/gamma(c)(null) mice. The same high engraftment rate of human mature cells was observed in ascites when peripheral blood mononuclear cells were intraperitoneally transferred. In addition to the high engraftment rate, multilineage cell differentiation was also observed. Further, even 1 x 10(2) CD34+ cells could grow and differentiate in this strain. These results suggest that NOD/SCID/gamma(c)(null) mice were superior animal recipients for xenotransplantation and were especially valuable for human stem cell assay. To elucidate the mechanisms involved in the superior engraftment rate in NOD/SCID/gamma(c)(null) mice, cytokine production of spleen cells stimulated with Listeria monocytogenes antigens was compared among these 3 strains of mice. The interferon-gamma production from dendritic cells from the NOD/SCID/gamma(c)(null) mouse spleen was significantly suppressed in comparison with findings in 2 other strains of mice. It is suggested that multiple immunological dysfunctions, including cytokine production capability, in addition to functional incompetence of T, B, and NK cells, may lead to the high engraftment levels of xenograft in NOD/SCID/gamma(c)(null) mice.
authors.affiliation: Central Institute for Experimental Animals, Department of Pediatrics, Graduate School of Medicine, Kyoto University, 1430 Nogawa, Miyamae, Kawasaki, Kanagawa 216-0001, Japan. mito@clea.or.jp
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Hiramatsu
authors.forename: Kimio
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazutomo
authors.initials: K
authors.lastname: Suzue
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawahata
authors.forename: Kyoji
authors.initials: K
authors.lastname: Hioki
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Tsuji
authors.forename: Toshio
authors.initials: T
authors.lastname: Heike
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000942:Antigens, Bacterial / Q000276:immunology; D001201:Ascites; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005677:G(M1) Ganglioside / Q000037:antagonists & inhibitors / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism; D053631:Interleukin Receptor Common gamma Subunit; D007694:Killer Cells, Natural / Q000473:pathology; D008089:Listeria monocytogenes / Q000276:immunology; D016131:Lymphocyte Subsets / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D023421:Models, Animal; D020395:Receptors, Interleukin-7 / Q000172:deficiency* / Q000235:genetics; D013154:Spleen / Q000473:pathology; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous / Q000276:immunology; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; C507941:IL2RG protein, human; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D020395:Receptors, Interleukin-7; D001613:beta 2-Microglobulin; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma