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      Clinical Chemistry of the Laboratory Mouse

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          The frontier of clinical chemistry in the mouse has advanced and expanded because of two major events such as, the increasing reliance on mice in biomedical research, and increasing availability of practical yet sophisticated techniques and instrumentations that have allowed for the detection of a wider variety of biomarkers of disease. The progression of these two events is partially driven by the increasing regulatory demands related to safety/toxicity assessment of novel drug development. The availability of inbred strains has led to major breakthroughs in cancer, biology, and immunology. In addition, outbred stocks continue to be utilized in a wide variety of studies but particularly in the fields of toxicology and pharmacology. The power of these models to elucidate the genetic basis of disease cannot be overemphasized. This provided complete nucleotide sequences for each genome allowing investigators to quickly develop the equivalent murine model for many of the inherited human diseases. Transgenic and knockout mice have helped clarify disease pathogenesis in virtually every area of medicine and often elucidated biochemical pathways, previously unknown, which are now subject to testing and quantification.

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          Of mice and not men: differences between mouse and human immunology.

          Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. However, as 65 million years of evolution might suggest, there are significant differences. Here we outline known discrepancies in both innate and adaptive immunity, including: balance of leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK inhibitory receptor families Ly49 and KIR, FcR, Ig subsets, the B cell (BLNK, Btk, and lambda5) and T cell (ZAP70 and common gamma-chain) signaling pathway components, Thy-1, gammadelta T cells, cytokines and cytokine receptors, Th1/Th2 differentiation, costimulatory molecule expression and function, Ag-presenting function of endothelial cells, and chemokine and chemokine receptor expression. We also provide examples, such as multiple sclerosis and delayed-type hypersensitivity, where complex multicomponent processes differ. Such differences should be taken into account when using mice as preclinical models of human disease.
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            Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.

            Fat tissue produces a variety of secreted proteins (adipocytokines) with important roles in metabolism. We isolated a newly identified adipocytokine, visfatin, that is highly enriched in the visceral fat of both humans and mice and whose expression level in plasma increases during the development of obesity. Visfatin corresponds to a protein identified previously as pre-B cell colony-enhancing factor (PBEF), a 52-kilodalton cytokine expressed in lymphocytes. Visfatin exerted insulin-mimetic effects in cultured cells and lowered plasma glucose levels in mice. Mice heterozygous for a targeted mutation in the visfatin gene had modestly higher levels of plasma glucose relative to wild-type littermates. Surprisingly, visfatin binds to and activates the insulin receptor. Further study of visfatin's physiological role may lead to new insights into glucose homeostasis and/or new therapies for metabolic disorders such as diabetes.
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              Diabetes mellitus: a "thrifty" genotype rendered detrimental by "progress"?

              J V Neel (1962)
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                Author and article information

                Journal
                The Mouse in Biomedical Research
                The Mouse in Biomedical Research
                2 September 2007
                2007
                2 September 2007
                : 171-216
                Affiliations
                Division of Comparative Medicine, MIT , Cambridge, MA
                The Jackson Laboratory, Bar Harbor, ME
                Laboratory Animal Research Center, The Rockefeller University, New York, NY
                Center for Comparative Medicine Schools of Medicine and Veterinary Medicine University of California Davis, CA
                Research Animal Resources and Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD
                School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
                Article
                B978-0-12-369454-6.50060-1
                10.1016/B978-012369454-6/50060-1
                7155603
                6ed95644-7448-4878-a197-b068a614e7a8
                Copyright © 2007 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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