Transgenics disease link

Lee, M.K. et al. Human a-synuclein-harboring familial Parkinson s disease-linked Ala-53 to Thr mutation causes neurodegenerative disease with a-synuclein aggregation in transgenic mice. Proc. Natl. Acad. Sci. USA 99 8968-8973, 2002. 

Zeron M. M., Fernandes H. B., Krebs C., Shehadeh J., Wellington C. L., Leavitt B. R., Baim-bridge K. G., Hayden M. R., and Raymond L. A. (2004). Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington s disease. Mol. Cell Neurosci. 25 469 179. 

There has been explosive growth in the number of disease models in recent decades, especially in the field of the knockouts and transgenic rodents. A description of the most frequently used models alone would take a separate volume, and even that would be outdated within no time. Information on the selection of models and background data can easily be found on the Internet. The US National Center for Research Resources (NCRR) provides overviews and links [12], In addition the main providers of laboratory animals have very useful information on their Web sites. Readers looking for overviews on animal models per disease may find useful information in the Drug Discovery Today Disease Models review journal (http //www.drugdiscoverytoday.com). 

Masliah E, Rockenstein E, Veinbergs I, Sagara Y, Mallory M, Hashimoto M, Mucke L (2001) p-Amyloid peptides enhance a-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer s disease and Parkinson s disease. Proc Natl Acad Sci USA 98 12245-12250. 

The second type of promoter polymorphism is a VNTR in the second intron composed of 17-bp repeats (Ogilvie et al., 1996). Ten and twelve sets of repeats are most common (Lesch et al., 1994). Studies with embryonic stem cells and transgenic embryos implicate the VNTR as playing a role in the regulation of transcription, although no definitive links are known between this VNTR and disease states (Torres et al., 2003a). 

Several human diseases are linked to imprinted genes. Genomic imprinting has also been demonstrated in transgenic mice. For example, transgenic mice with the gene for... 

Link CD. 2001. Transgenic invertebrate models of age-associated neurodegener-ative diseases. Mech. Ageing Dev. 122 1639-49... 

The central role of PrPc in the pathogenesis of prion diseases was demonstrated in transgenic mice with a targeted disruption of the PrP gene PrP0/0 mice are resistant to prion diseases and do not propagate infectious prions [32]. Moreover, inherited prion diseases in humans are causally linked to mutations in Pmp (reviewed in [22, 33]). 

DNA-binding domain. This polyQ-expanded TBP, incapable of binding DNA, formed nuclear inclusions and caused a severe neurological phenotype in transgenic mice. Together, these results indicate that polyQ-expanded TBP is inhibitory to TATA-dependent transcription as it is unable to bind DNA productively [181,182]. PolyQ-expanded Htt exon 1 protein has also been shown to bind and sequester TBP [183]. In the case of mutant ataxin-7, HAT activity of the STAGA complex is compromised, and this has been directly linked to the retinal degeneration common in this disease [184, 185]. Transcriptional abnormalities have also been detected in ALS patients and mouse models thereof [186-188]. 

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