What are nod scid mice3/29/2024 ![]() ![]() It has been known for over a decade that immunodeficient mice with the NOD background engraft human hematopoietic stem cells (HSCs) more efficiently than immunodeficient mice on other genetic backgrounds. The race to develop even more advanced NOD-derived immunodeficient mice has been fueled by the need to develop “humanized” mice – that is, mice that express fully functional human immune cells in place of their murine counterparts. The Sirpa NOD allele promotes engraftment of human hematopoietic stem cells (hHSCs) in NOD-derived immunodeficient mice. Indeed, NOD- scid mice support as much as 5-fold higher levels of human lymphoid cell engraftment, in comparison to for example C.B-17- scid mice. ![]() 2003).Ĭombined, the above attributes make the NOD genetic background an ideal platform that, in combination with the scid mutation, produces mice that support better engraftment of human-derived immune cells. Antigen-presenting dendritic cells in NOD mice also show maturation defects ( Pearson et al. Macrophages from NOD inbred mice retain many of the characteristics of immature cells macrophages and have weak functional responses ( Serreze et al. The subsequent displaying of antigens derived from the pathogens on the APC’s cell surface is key in triggering adaptive immune responses. Macrophages and APCs are immune cells that are important in engulfing pathogens. Therefore, the reduced NK cell function in NOD mice greatly improves engraftment of human cells.ģ) Differentiation and functional deficits in macrophages and antigen presenting cells (APCs). Importantly, NK cell activity is a major impediment to the engraftment of human hematopoietic cells in mice. NK cells are a class of cytotoxic cells in the innate immune system that rapidly respond to virally infected cells in the absence of antibodies. In comparison to BALB/c and C.B-17 mice, NOD inbred mice have severely reduced NK cell activity ( Kataoka et al. Without functional C5, complement proteins fail to assemble, and invading pathogens escape their damaging effects.Ģ) Defective Natural Killer (NK) cells. NOD mice, as well as several other inbred strains, are homozygous for a deletion in the hemolytic complement ( Hc) gene that prevents Hc (aka C5) complement protein expression. Normally, a subgroup of complement proteins forms complexes that poke holes in a pathogen’s cellular membrane and lyse the invading cell. The complement system is a multiple protein-based component of the innate immune system that assists antibodies and phagocytic cells in destroying and clearing pathogens from the host. NOD inbred mice are characterized by the following inherent immune deficiencies:ġ) Absence of circulating complement. Inherent immune deficiencies in NOD mice that augment genetically induced immune deficiencies It turns out that NOD inbred mice have inherent deficiencies in key humoral and cellular immune cell activities that enhances the overall immune deficiency of NOD- scid mice in comparison to C.B-17- scid or C57BL/6- scid (B6.CB17- Prkdc scid/SzJ) –mice. The likely explanation for their limited engraftment capacity is that C.B-17- scid mice retain normal NK and myeloid cell function. Although C.B-17- scid mice are both T and B cell deficient, they fail to support long-term engraftment of the human immune cells that are critical for developing small animal models for human infectious diseases such as HIV. The Prkdc scid is a spontaneous mutation initially characterized in a BALB/c congenic strain called C.B-17. As a result, they are the perfect hosts for the adoptive transfer of T and B cells from diabetic NOD mice to investigate their roles in the development of autoimmune (Type 1) diabetes.Ģ) The development of a mouse that would support long-term engraftment of human cells and tissues for studies related to human infectious disease and cancer. Two distinct research goals drove the development of NOD immunodeficient models:ġ) The development of a mouse that could be used to uncover which immune cells actually drive the development of autoimmune diabetes in NOD mice.Īs outlined in a recent post, NOD-scid mice (NOD.CB17- Prkdc scid/J), because they are B and T cell-deficient, do not develop diabetes. How exactly did this happen? Immunodeficient NOD mice advance both diabetes and human infectious disease research ![]() It strikes me as strange that this strain would become the background of choice in the development of Nod Scid Gamma (NSG) and other severely immunodeficient mice that have revolutionized the development of next-generation human cancer and infectious disease models. Dear JAXY: Why is NOD the preferred genetic background for immune-deficient mice?Īs we discussed in an earlier post, non-obese diabetic (NOD/ShiLtJ) mice are one of the most commonly used mice to model insulin-dependent (Type I) diabetes. ![]()
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