A genetic dissection of brain and heart phenotypes in the Tc1 transchromosomic mouse model of Down syndrome. (360G-Wellcome-080174_Z_06_Z)

£606,749

Down syndrome (DS) arises from trisomy of human chromosome 21 (Hsa21), and thus from an abnormal gene dosage of unmutated Hsa21 genes, giving rise to the many phenotypes that are found in DS individuals. However, it remains unknown which genes need to be present in three copies to cause particular phenotypes, such as heart malformation. The genotype-phenotype relationships in DS have proven extremely difficult to tease out, yet are important as individuals with DS succumb to a range of disorders such as dementia, heart disorders, etc., that may be treatable if we know which cellular pathways are involved.We have recently established a novel transchromosomic mouse model of DS termed Tc1, which carries a freely segregating Hsa21. Tc1mice have defects in behaviour, synaptic plasticity, and brain and heart development. We now propose to investigate these brain and heart defects in much more depth and to combine this with chromosome engineering of mouse embryonic stem cells to dissect the molecular genetics of these phenotypes. We will combine our knowledge of mouse embryonic stem cell manipulation and the creation of transchromosomic mice, with specialist knowledge from three laboratories studying brain and heart. Working together, we will initially map regions of Hsa21 and ultimately identify specific genes which when present in three copies are responsible for the brain and heart phenotypes.

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Grant Details

Amount Awarded 606749
Applicant Surname Fisher
Approval Committee Molecules, Genes and Cells Funding Committee
Award Date 2006-06-27T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Programme Grant
Internal ID 080174/Z/06/Z
Lead Applicant Prof Elizabeth Fisher
Other Applicant(s) Prof Victor Tybulewicz
Partnership Value 606749
Planned Dates: End Date 2014-02-28T00:00:00+00:00
Planned Dates: Start Date 2007-03-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London