NOG mouse

A NOG (NOD/Shi-scid/IL-2Rγ^null) mouse is a new generation of severely immunodeficient mouse, developed by Central Institute for Experimental Animals (CIEA) in 2000. The NOG mouse accepts heterologous cells much more easily compared with any other type of immunodeficient rodent models, such as, nude mouse and NOD/scid mouse. Thus, the mouse can be the best model as a highly efficient recipient of human cells to engraft, proliferate and differentiate.^[1] This unique feature offers a great opportunity for enhancing therapy researches of cancer, leukemia, visceral diseases, AIDS, and other human diseases. It also provides applications for cancer, infection, regeneration, and hematology researches.

Origin

The NOG mouse was generated in CIEA in 2000 by back-cross mating of C57BL/6J-IL-2Rγ^null mouse that was originally developed by Kazuo Sugamura, a professor of Tohoku University, to NOD/Shi-scid mouse that was developed in CIEA.

Characteristics

No activity of T cell, B cell and NK cell
Reduced complementary activities
Dysfunction of macrophage
Dysfunction of dendritic cell
No leakiness: no incidence of T, B cells with aging
No incidence of lymphoma

NOG mouse has multiple immunodeficiencies that are principally derived from three strains of mice: 1) NOD/Shi inbred strain, 2) SCID, 3) IL-2Rγ^null. These include:

Reduced innate immunity derived from a NOD inbred strain, which involves a macrophage dysfunction, and a defect of complement hemolytic activity and reduced NK activity.^[2] The NOD/Shi inbred strain was first discovered by Makino et al. as autoimmune non-obese-type diabetes mice.^[3]^[4]
Lack of functional T and B cells that is derived from a mutation of protein kinase (Prkdc: protein kinase, DNA activated, catalytic polypeptide), which is the causative gene of the scid mutation ^[5]^[6]
Lack of NK cells, dendritic cell dysfunctions, and other unknown deficiencies due to inactivation of the IL-2Rγ gene.^[7]^[8]^[9]^[10]

Applications to medical researches

Cancer
Infectious Diseases
Regenerative Medicine
Hematology
Humanized mouse

References

↑ M. Ito and et al. (2002). "NOD/SCID/γ^null mouse: an excellent recipient mouse model for engraftment of human cells". Blood 100 (9): 3175–3182. doi:10.1182/blood-2001-12-0207. PMID 12384415.
↑ Shultz, L. D.; Schweitzer, P. A.; Christianson, S. W.; Gott, B.; Schweitzer, I. B.; Tennent, B.; McKenna, S.; Mobraaten, L.; Rajan, T. V. et al. (1995). "Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice". Journal of Immunology 154 (1): 180–191. PMID 7995938.
↑ Kikutani, H.; Makino, S. (1992). "The murine autoimmune diabetes model: NOD and related strains". Adv Immunol. Advances in Immunology 51: 285–322. doi:10.1016/S0065-2776(08)60490-3. ISBN 9780120224517. PMID 1323922.
↑ Makino, S.; Kunimoto, K.; Muraoka, Y.; Mizushima, Y.; Katagiri, K.; Tochino, Y. (1980). "Breeding of a non-obese, diabetic strain of mice". Jikken Dobutsu 29 (1): 1–13. PMID 6995140.
↑ Bosma, G. C.; Custer, R. P.; Bosma, M. J. (1983). "A severe combined immunodeficiency mutation in the mouse". Nature 301 (5900): 527–530. doi:10.1038/301527a0. PMID 6823332.
↑ Kirchgessner, C. U.; Patil, C. K.; Evans, J. W.; Cuomo, C. A.; Fried, L. M.; Carter, T.; Oettinger, M. A.; Brown, J. M. (1995). "DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect". Science 267 (5201): 1178–1183. doi:10.1126/science.7855601. PMID 7855601.
↑ Ikebe, M.; Miyakawa, K.; Takahashi, K.; Ohbo, K.; Nakamura, M.; Sugamura, K.; Suda, T.; Yamamura, K.; Tomita, K. et al. (1997). "Lymphohaematopoietic abnormalities and systemic lymphoproliferative disorder in interleukin-2 receptor gamma chain-deficient mice". Int J Exp Pathol 78 (3): 133–148. PMC 2694530. PMID 9306921.
↑ Ohbo, K.; Suda, T.; Hashiyama, M.; Mantani, A.; Ikebe, M.; Miyakawa, K.; Moriyama, M.; Nakamura, M.; Katsuki, M. et al. (1996). "Modulation of hematopoiesis in mice with a truncated mutant of the interleukin-2 receptor gamma chain". Blood 87 (3): 956–967. PMID 8562967.
↑ Ohteki, T.; Fukao, T.; Suzue, K.; Maki, C.; Ito, M.; Nakamura, M.; Koyasu, S. (1999). "Interleukin-12 dependent interferon-g production by CD8a + lymphoid dendritic cells". J Exp Med 189 (12): 1981–1986. doi:10.1084/jem.189.12.1981. PMC 2192968. PMID 10377194.
↑ Sugamura, K.; Asao, H.; Kondo, M.; Tanaka, N.; Ishii, N.; Ohbo, K.; Nakamura, M.; Takeshita, T. (1996). "The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID". Annu Rev Immunol 14: 179–205. doi:10.1146/annurev.immunol.14.1.179. PMID 8717512.

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