Both Rag2 and Rag1 bind DNA at recombination signal sequences and create single strand nicks as the first step of recombination. The Rag2 protein is also involved in V(D)J recombination. The Rag2 gene, recombination activating gene 2, was knocked out in 1992 by Frederick Alt at Columbia University 6. Rag2 knockouts are somewhat lesser known compared to scid mice but offer numerous advantages. The basic mechanism of V(D)J recombination. When using drugs with this type of mechanism, a tolerance study is recommended to help choose appropriate doses for follow on efficacy studies. Scid mice may also be more sensitive to drugs which damage DNA. They are thus not ideal choices for experiments involving clinically relevant radiation doses. As this mutation affects DNA repair, mice carrying Prkdc scid are more sensitive to radiation. The scid mutation introduces a few other special considerations. Longer term studies are not advisable in the NOD scid strain. The major drawback to the NOD scid is that it develops thymic lymphomas at a high rate, so the effective lifespan is somewhere between 7-9 months. This makes it the most immunocompromised of the basic scid models. They are also on the less leaky end of the spectrum. NOD mice lack complement C5, and they have defects in macrophage and dendritic cell function. The NOD scid is special in that the NOD inbred strain background imparts some additional immunodeficiency. In general, the ICR scid is an excellent value. Note that larger animals also require additional compound for dosing. However, the outbred background can introduce more experimental variation. As an outbred, ICR scid mice are larger, hardier and less expensive. The ICR scid is a less leaky alternative on an outbred background. While the C.B-17 scid may be fine for short term experiments, longer term experiments may be challenging. In C.B-17- scid (6-9 months old) mice, serum IgG+M+A antibody levels measured in 1989 were used in this figure. IgG+M antibody levels in the sera from aged NOG (7-10 months old) and NOD-scid (6-7 months old) mice were measured by ELISA. This leakiness varies by the strain/stock background, with age and by housing conditions, with the original C.B-17 scid actually being the leakiest strain. This appears to arise from a low frequency of V(D)J coding joint formation, with recombination often occurring at sections of short homology 5. Scid mice can become "leaky", meaning that some functional T and B cells can develop. But it may not always be the best experimental choice.ĭevelopment of some functional T and B cells Among the scids that Taconic Biosciences offers, the C.B-17 scid is the most requested, primarily due to the wealth of historical data and publications using the strain. The Prkdc scid allele was also backcrossed onto other strain and stock backgrounds to make models such as the outbred ICR scid and the NOD scid. As one of the first immunodeficient models available, that original scid, the C.B-17 scid, was disseminated worldwide and has been used in thousands of studies. V(D)J recombination, which rearranges the genetic components of antibodies and T cell receptors during B and T cell development, requires NHEJ for proper function.ĭue to the NHEJ defect in Prkdc scid mutants, scid mice lack both mature T and B cells. Prkdc is involved in DNA repair via non-homologous end joining (NHEJ). The specific genetic alteration in the Prkdc scid allele is an T-to-A transversion point mutation at codon 4095, which creates a premature stop codon 2, 3. The scid mutation is a mutation in the Prkdc gene, protein kinase, DNA activated, catalytic polypeptide. This mutation arose spontaneously in a colony of C.B-17 mice that Bosma was using for studies of immunoglobulin isotypes. Scid stands for severe combined immunodeficiency. The scid mutation was first discovered in 1983 by Mel Bosma at the Fox Chase Cancer Center 1. Learn more about two key immunodeficient models, scid mutants and Rag2 knockouts, and how to choose the most appropriate model for your study. Although these models are used quite widely, not all researchers understand their intrinsic characteristics and how those characteristics impact experimental outcomes. Starting with the discovery of athymic nude mice in the 1960's, the portfolio of immunodeficient rodents has grown significantly. Mice with compromised immune systems are invaluable research tools.
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