The NSG mouse (NOD scid gamma mouse) is a brand of immunodeficient laboratory mice, developed and marketed by Jackson Laboratory, which carries the strain NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ. NSG branded mice are among the most immunodeficient described to date. [1] NSG branded mice lack mature T cells, B cells, and natural killer (NK) cells. [2] NSG branded mice are also deficient in multiple cytokine signaling pathways, and they have many defects in innate immunity. [2] [3] The compound immunodeficiencies in NSG branded 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 branded mice were developed in the laboratory of Dr. Leonard Shultz at Jackson Laboratory, which owns the NSG trade mark.
Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in differing clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.
Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene localized on chromosome 5q31.1. Sometimes also called colony-stimulating factor, multi-CSF, mast cell growth factor, MULTI-CSF, MCGF; MGC79398, MGC79399: the protein contains 152 amino acids and its molecular weight is 17 kDa. IL-3 is produced as a monomer by activated T cells, monocytes/macrophages and stroma cells. The major function of IL-3 cytokine is to regulate the concentrations of various blood-cell types. It induces proliferation and differentiation in both early pluripotent stem cells and committed progenitors. It also has many more specific effects like the regeneration of platelets and potentially aids in early antibody isotype switching.
Omenn syndrome is an autosomal recessive severe combined immunodeficiency. It is associated with hypomorphic missense mutations in immunologically relevant genes of T-cells such as recombination activating genes, Interleukin-7 receptor-α (IL7Rα), DCLRE1C-Artemis, RMRP-CHH, DNA-Ligase IV, common gamma chain, WHN-FOXN1, ZAP-70 and complete DiGeorge syndrome. It is fatal without treatment.
The common gamma chain (γc), also known as interleukin-2 receptor subunit gamma or IL-2RG, is a cytokine receptor sub-unit that is common to the receptor complexes for at least six different interleukin receptors: IL-2, IL-4, IL-7, IL-9, IL-15 and interleukin-21 receptor. The γc glycoprotein is a member of the type I cytokine receptor family expressed on most lymphocyte populations, and its gene is found on the X-chromosome of mammals.
Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene.
X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells.
Non-obese diabetic or NOD mice, like biobreeding rats, are used as an animal model for type 1 diabetes. Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. The onset of diabetes is associated with a moderate glycosuria and a non-fasting hyperglycemia. It is recommended to monitor for development of glycosuria from 10 weeks of age; this can be carried out using urine glucose dipsticks. NOD mice will develop spontaneous diabetes when left in a sterile environment. The incidence of spontaneous diabetes in the NOD mouse is 60–80% in females and 20–30% in males. Onset of diabetes also varies between males and females: commonly, onset is delayed in males by several weeks.
Non-receptor tyrosine-protein kinase TYK2 is an enzyme that in humans is encoded by the TYK2 gene.
Tyrosine-protein kinase JAK3 is a tyrosine kinase enzyme that in humans is encoded by the JAK3 gene.
The severe combined immunodeficiency (SCID) is a severe immunodeficiency genetic disorder that is characterized by the complete inability of the adaptive immune system to mount, coordinate, and sustain an appropriate immune response, usually due to absent or atypical T and B lymphocytes. In humans, SCID is colloquially known as "bubble boy" disease, as victims may require complete clinical isolation to prevent lethal infection from environmental microbes.
CD47 also known as integrin associated protein (IAP) is a transmembrane protein that in humans is encoded by the CD47 gene. CD47 belongs to the immunoglobulin superfamily and partners with membrane integrins and also binds the ligands thrombospondin-1 (TSP-1) and signal-regulatory protein alpha (SIRPα). CD-47 acts as a don't eat me signal to macrophages of the immune system which has made it a potential therapeutic target in some cancers, and more recently, for the treatment of pulmonary fibrosis.
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
A NOG (NOD/Shi-scid/IL-2Rγnull) 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. 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.
A humanized mouse is a mouse carrying functioning human genes, cells, tissues, and/or organs. Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics.
Interleukin-7 receptor subunit alpha (IL7R-α) also known as CD127 is a protein that in humans is encoded by the IL7R gene.
Immunity Related Guanosine Triphosphatases or IRGs are proteins activated as part of an early immune response. IRGs have been described in various mammals but are most well characterized in mice. IRG activation in most cases is induced by an immune response and leads to clearance of certain pathogens.
Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). As these cells are short-lived, there needs to be a steady turnover of new blood cells and the maintenance of an HSC pool. This is broadly termed hematopoiesis. This event requires a special environment, termed the hematopoietic stem cell niche, which provides the protection and signals necessary to carry out the differentiation of cells from HSC progenitors. This niche relocates from the yolk sac to eventually rest in the bone marrow of mammals. Many pathological states can arise from disturbances in this niche environment, highlighting its importance in maintaining hematopoiesis.
Patient derived xenografts (PDX) are models of cancer where the tissue or cells from a patient's tumor are implanted into an immunodeficient or humanized mouse. PDX models are used to create an environment that allows for the natural growth of cancer, its monitoring, and corresponding treatment evaluations for the original patient.
Mice with severe combined immunodeficiency (SCIDs) are often used in the research of human disease. Human immune cells are used to develop human lymphoid organs within these immunodeficient mice, and many different types of SCID mouse models have been developed. These mice allow researchers to study the human immune system and human disease in a small animal model.
The laboratory mouse has been instrumental in investigating the genetics of human disease, including cancer, for over 110 years. The laboratory mouse has physiology and genetic characteristics very similar to humans providing powerful models for investigation of the genetic characteristics of disease.