Lecture8DownSyndrome

Iq in segmental trisomy 21 conclusions from korbel et

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IQ in segmental trisomy 21: conclusions from Korbel et al. study New evidence for a 4.6 Mb telomeric region of HSA21 that may contribute to mental retardation in DS. Six of seven persons with three copies of regions that include the telomeric 4.6 Mb are of lowest cognitive function (lowest IQ ` s) Sources and further reading: Gardiner KJ (2010 ) Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci. 2010 Feb;31(2):66-73 Rachidi M, Lopes C.(2007) Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms. Neurosci Res. 59(4): 349-69 Find these articles on PubMed: http://www.ncbi.nlm.nih.gov/pubmed
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Mouse models of DS Used to study - the mechanisms of the disease - Test possible treatments Challenge: Genes from human Chromosome 21 in mice: Chromosome 16 (26.5 Mb) Chromosome 10 (~2.3 Mb) Chromosome 17 (1.1 Mb)
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Ts65Dn mouse is the most commonly used model of Down Syndrome Mouse arLfcial chromosomes Ts65Dn chromosome: translocaLon oF mouse chromosome 16 and a small part oF Chr. 17, carries ~ 140 genes orthologous to human genes on Chr. 21 Phenotype oF Ts65Dn mice: cranioFacial phenotype, reduced spaLal learning and memory, reduced cerebellum volume, degeneraLon oF B±CN ` s Ts1Cje mouse: similar to Ts65Dn, slightly milder Most oF mouse orthologs oF human chromosome 21 gene are located on mouse chromosome 16.
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How do you assay cognitive defects in mice? Example: Morris Water Maze http://www.youtube.com/watch?v=LrCzSIbvSN4
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Many therapies are currently being tested on Ts65Dn mice One example: Neuroinflammation may be a contributing factor to neurodegeneration in DS. Ts65Dn mice show elevated level of neuroinflammatory markers Minocycline – anti-inflammatory drug, in clinical trials for Parkinson ` s and Huntington ` s diseases Ts65Dn mice were treated with minocycline for 75 days from 7 months of age Results: improved (though still not normal) performance on water maze, less BFCN degeneration From: Gardiner KJ (2010 ) Molecular basis of pharmacotherapies for cognition in Down syndrome. Trends Pharmacol Sci. 2010 Feb;31(2):66-73
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Which of the following mouse models will allow you to answer the question if DSCAM contributes to the decrease in spatial memory in DS? A. Transgenic mouse carrying an extra copy of DSCAM gene B. A mouse carrying a homozygous knockout of DSCAM C. A conditional knockout mouse crossed in which Cre is driven by a brain-specific promoter D. Ts65Dn mouse
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IQ in segmental trisomy 21 conclusions from Korbel et al...

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