Six of seven persons with three copies of regions

Info icon This preview shows pages 24–29. Sign up to view the full content.

View Full Document Right Arrow Icon
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:
Image of page 24

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
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)
Image of page 25
Ts65Dn mouse is the most commonly used model of Down Syndrome Mouse arLficial 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 BFCN s Ts1Cje mouse: similar to Ts65Dn, slightly milder Most of mouse orthologs of human chromosome 21 gene are located on mouse chromosome 16.
Image of page 26

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
How do you assay cognitive defects in mice? Example: Morris Water Maze
Image of page 27
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
Image of page 28

Info icon This preview has intentionally blurred sections. Sign up to view the full version.

View Full Document Right Arrow Icon
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
Image of page 29
This is the end of the preview. Sign up to access the rest of the document.

{[ snackBarMessage ]}

What students are saying

  • Left Quote Icon

    As a current student on this bumpy collegiate pathway, I stumbled upon Course Hero, where I can find study resources for nearly all my courses, get online help from tutors 24/7, and even share my old projects, papers, and lecture notes with other students.

    Student Picture

    Kiran Temple University Fox School of Business ‘17, Course Hero Intern

  • Left Quote Icon

    I cannot even describe how much Course Hero helped me this summer. It’s truly become something I can always rely on and help me. In the end, I was not only able to survive summer classes, but I was able to thrive thanks to Course Hero.

    Student Picture

    Dana University of Pennsylvania ‘17, Course Hero Intern

  • Left Quote Icon

    The ability to access any university’s resources through Course Hero proved invaluable in my case. I was behind on Tulane coursework and actually used UCLA’s materials to help me move forward and get everything together on time.

    Student Picture

    Jill Tulane University ‘16, Course Hero Intern