NSG mouse
Encyclopedia
NSG, or NOD scid gamma, is among the most immunodeficient strains of inbred laboratory mice described to date. NSG mice lack mature T cells, B cells, and natural killer (NK) cells. NSG mice are also deficient in multiple cytokine
signaling pathways, and they have many defects in innate immunity. The compound immunodeficiencies in NSG mice permit the engraftment of a wide range of primary human cells, and enable sophisticated modeling of many areas of human biology and disease. NSG mice were developed in the laboratory of Dr. Leonard Shultz at The Jackson Laboratory.
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
signaling pathways, and they have many defects in innate immunity. The compound immunodeficiencies in NSG mice permit the engraftment of a wide range of primary human cells, and enable sophisticated modeling of many areas of human biology and disease. NSG mice were developed in the laboratory of Dr. Leonard Shultz at The Jackson Laboratory.
Features of NSG mice
- The genetic background, derived from inbred NOD mouse strain NOD/ShiLtJ, contributes reductions in innate immunity that include an absent hemolytic complement systemComplement systemThe complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
, reduced dendritic cellDendritic cellDendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
function, and defective macrophageMacrophageMacrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
activity. The NOD/ShiLtJ background also contributes an allele of the Sirpa gene that renders the bone marrow niche very permissive to colonization by human hematopoietic stem cells. - The Prkdcscid mutation, commonly known as “scid” or “severe combined immunodeficiencySevere combined immunodeficiencySevere combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
”, essentially eliminates adaptive immunity. Prkdcscid is a loss-of-function mutation in the mouse homologue of the human PRKDCPRKDCDNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the PRKDC gene. DNA-PKcs belongs to the phosphatidylinositol 3-kinase-related kinase protein family.- Function :...
gene, which encodes a protein that resolves DNA strand breaks that occur during V(D)J recombinationV(D)J recombinationVJ recombination, also known as somatic recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin and T cell receptors production of the immune system...
in developing T and B lymphocytes. Mice homozygous for the mutation have severely reduced numbers of mature T and B cells. The phenotypic penetrance of Prkdcscid varies among inbred strain backgrounds, but the mutation is most effective at eliminating adaptive immunity on the NOD genetic background. - The Il2rgtm1Wjl targeted mutation is a complete null mutation in the gene encoding the interleukin 2 receptor gamma chain (IL2Rγ, homologous to IL2RG in humans). IL2Rγ is a common component of the cell surface receptors that bind and transduce signals from six distinct interleukins. Signaling through IL2Rγ is required for the differentiation and function of many hematopoietic cells. Notably, the absence of IL2Rγ blocks NK cell differentiation, and thereby removes a major obstacle preventing the efficient engraftment of primary human cells.
Research applications of NSG include
- Primary human lung tumor xenografts that preserve the tumor microenvironment during long-term engraftment
- Models of acute or chronic leukemia established using cancer cells collected from patients (A complete list of publications is available here)
- A highly sensitive platform for studying epithelial and cancer stem cells
- Establishing a functional, humanized immune system from engrafted human hematopoietic stem cells and progenitors
- Humanized models for studying human-specific infectious diseases like HIVHIVHuman immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, Epstein Barr virus , malariaMalariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
, and Dengue feverDengue feverDengue fever , also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles...
. Humanized models also aid in testing new therapies - Studying allograft rejection after pancreatic islet transplantation therapy for type 1 diabetes