Model mouse

The U.S. standard pertussis vacciae is used to standardize the potency of the whole ceU pertussis vacciae. The number of protective units Hi the vaccine is estimated for each lot from the results of simultaneous intracerebral mouse-protection tests of the vaccine being studied and the U.S. reference standard (14,17). The potency of the aceUular vaccines is estimated by then abUity to produce antibodies to the proteins Hi the vaccine Hi a mouse model. These vaccines also undergo a series of animal safety tests to ensure that the iaactivation and toxoiding steps were carried out correctiy (14,17). 

Arap W, Pasqualini R, Ruoslahti E (1998) Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science 279 377-380... 

Chan CS, Guzman JN, Ihij ic E, Mercer JN, Rick C, Tkatch T, Meredith GE, Sunneier DJ (2007) Rejuvenation protects neurons in mouse models of Parkinson s disease. Nature 447 1081-1086... 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

Vertex also put in clinical trial VX-765, another caspase-1 -specific, YVAD-derived peptidomimetic that is in vitro slightly more potent then pralnacasan (IC50 0.8 nM). Evaluation of VX-765 in a mouse model of oxazolone-induced dermatitis showed a dose-dependent (10-100 mg/kg) inhibition of ear inflammation. Consequently, VX-765 was enrolled in a 4-week phase Ila safety and pharmacokinetic study for psoriasis. However, Vertex has not communicated any results yet. 

The physiological roles of these channels are apparent from human diseases or mouse models in which these genes are disiupted. 

HSV2 (herpes simplex virus 2), which causes significant morbidity and is an important cofactor for the transmission of HIV infection was recently targeted in a mouse model by local application of siRNA mixed with lipids. The results suggested that siRNA could work as active components of microbicides to prevent viral infection or transmission [2]. 

Harper SQ, Staber PD, He X et al (2005) RNA interference improves motor and neuropathological abnormalities in a Huntington s disease mouse model. Proc Natl Acad Sci USA 102(16) 5 820-5 825... 

Furthermore, we also found behaviour differences in our mouse models of S100A1 deficiency. The male S100A1 knockout, mice showed reduced anxiety-like responses and enhanced explorative activities and we concluded that S100A1 plays a role in modulating innate fear and exploration of novel stimuli. 

SUMOl haploinsufficiency has been linlced to a developmental defect Based on the finding that a patient with a cleft lip and palate had a mutation in the SUMOl gene locus, a mouse model was generated that had reduced SUMOl expression. Increased frequency for a cleft palate or oblique facial cleft was observed in the transgenic mice, suggesting that SUMO haploinsufficiency can lead to developmental defects. 

In a mouse model for autoimmune non-obese diabetes (NOD), the full-blown diabetes could be reversed to normoglycaemia by treatment with CD3 antibodies. In these diabetes- tolerant mice, the proportions of CD4+ CD25+ regulatory T cells were increased. Moreover, the CD4+ CD25+ regulatory T cells of the tolerant mice produced high levels of... 

Morrissey DV, Blanchard K, Shaw L, Jensen K, Lockridge JA, Dickinson B, McSwiggen JA, Vargeese C, Bowman K, Shaffer CS, Pohsky BA, Zinnen S (2005a) Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 41 1349-1356... 

In addition, stndies evaluating interferon alpha/beta and interlenkin-16 expression have shown snbstantial antiviral effects against HlV-1 in vitro and in a humanized mouse model (Cremer et al. 2000 Lanret et al. 1994 Sanhadji et al. 1997 Zhou etal. 1997). 

Bai J, Gorantla S, Banda N, Gagnon L, Rossi J, Akkina R (2000) Characterization of anti-CCR5 ribozyme-transduced CD34-I- hematopoietic progenitor cells in vitro and in a SCID-hu mouse model in vivo. Mol Ther 1 244—254... 

Wuyts A, Overbergh L, Mathieu C, Ceuppens JL Interleukin-17 orchestrates the granulocyte influx into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol 2003 28 42-50. 

This chapter highlights the mechanisms responsible for mast cell activation during anaphylactic responses to environmental substances. In addition to discussing in detail the activation of mast cells and basophils by IgE and antigen, we also will describe how mouse models have been used to analyze the importance of various proteins, cells, mediators and activation mechanisms in the expression of anaphylaxis in that species. 

Although human anaphylaxis is a systemic reaction, the mouse model of passive cutaneous anaphylaxis (PGA) has been used extensively to enhance our understanding of mechanisms which also may contribute to systemic anaphylaxis. Unlike systemic anaphylaxis in the mouse, PGA appears to be entirely dependent on mast cells [4,6]. While IgE appears to be the primary antibody isotype that mediates PCA reactions in actively immunized mice, activation of FcyRIII by a fraction of IgGl antibodies (called anaphylactic IgGl) can also mediate PCA reactions in mice [4]. 

Finkelman FD Anaphylaxis lessons from mouse models. J Allergy Clin Immunol 2007 120 506-515. 

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