Identification of a set of genes showing regionally enriched expression in the mouse brain.
BACKGROUND
The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain.


RESULTS
We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology.


CONCLUSIONS
Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression.
D'Souza
Cletus A
CA
Genome Sciences Centre, British Columbia Cancer Agency, 570 West 7th Ave - Suite 100, Vancouver, BC, V5Z 4E6, Canada. cdsouza@bcgsc.ca
Chopra
Vikramjit
V
Varhol
Richard
R
Xie
Yuan-Yun
YY
Bohacec
Slavita
S
Zhao
Yongjun
Y
Lee
Lisa L C
LL
Bilenky
Mikhail
M
Portales-Casamar
Elodie
E
He
An
A
Wasserman
Wyeth W
WW
Goldowitz
Daniel
D
Marra
Marco A
MA
Holt
Robert A
RA
Simpson
Elizabeth M
EM
Jones
Steven J M
SJ
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D017403:In Situ Hybridization; D008297:Male; D015201:Meta-Analysis as Topic; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger