Mouse transgenic

ALUMDIUMCOPTPOUNDS - ALUMINUM SULFATE AND ALUMS] pol 2) -in transgenic mice [GENETIC ENGINEERING - ANIPLALS] pol 12)... 

Many human diseases are caused when certain proteins are either over- or underexpressed. Eor example, breast cancer can be induced by overexpressing certain cellular oncogenes within mammary tissue. To study the disease, researchers produce a line of transgenic mice that synthesize an abnormal amount of the same protein. This leads to symptoms of the disease in mice that are similar to what is found in humans. A protein can be overexpressed by inserting a DNA constmct with a strong promotor. Conversely, underexpression of a protein can be achieved by inserting a DNA constmct that makes antisense RNA. This latter blocks protein synthesis because the antisense RNA binds and inactivates the sense mRNA that codes for the protein. Once a line of mice is developed, treatments are studied in mice before these therapies are appHed to humans. 

Peterson, K. R., et al., 1997. Production of transgenic mice widi yeast artificial chromo.somes. Trends in Genetics 13 61-66. 

Amyotropic lateral sclerosis (ALS) 3. AEA and 2-AG increase in the spinal cord of SOD1 transgenic mice, a model of ALS, to inhibit disease progress 3. CB2 receptor agonists or inhibitors of degradation... 

Hirschsprung s disease have ETB receptor mutations). The lack of ET-3/ETB receptor results in the absence of parasympathic ganglionic neurons in the myenteric plexus (Auerbach). Mice with an ET-3/ETB receptor disruption die within 2 weeks after birth. In transgenic mice, in which the expression of the ETB receptor is driven by the dopamine (3-hydroxylase promoter, normal myenteric plexus are present and no enteric disorder develops. These mice, however, show a salt-sensitive hypertension, which can be efficiently treated with amiloride, indicating that ETB receptors are involved in the regulation of natriuresis via the amilorid-sensitive sodium channel ENaC. 

Pepin et al. (1992) generated transgenic mice in which antisense RNA complementary to GR cDNA led to reduced expression mostly in neuronal tissues. Consequently, this was found to result in an impaired behavior, a defective response to stress as well as in obesity. King et al. (1995) generated transgenic mice where reduced GR expression was limited to the thymus. This leads to an altered thymocyte development, changes in the T-cell repertoire, and a reduced risk to develop autoimmune diseases. 

As additional tools, transgenic mice overexpressing NPY and knockout mice lacking NPY, Yi receptors or Y5 receptors have been published. 

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. 

We have gained considerable insight into the therapeutic potential of this protein through the use of TGF-(3 antagonists and transgenic mice with defective TGF-(3 signaling and we have evaluated the potential toxicity of TGF-(3 modulation and its overall efficacy in treating cancer. FC Soluble Type II Receptor... 

Kistner A, Gossen M, Zimmermann F et al (1996) Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 93 10933-10938... 

Muth JN, Varadi G, Schwartz A (2001) Use of transgenic mice to study voltage-dependent Ca2+ channels. Trends Pharmacol Sci 22 526-532... 

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