Update by Adrian Bird
This laboratory’s Jeans for Genes funding via
RSAUK commenced 1 April 2004. Our work focuses on studies of a mouse model
of Rett syndrome that was created in the lab three years ago. The mouse
shows several features that parallel RTT in humans. Mice completely lacking
MeCP2 (Mecp2-null mice) are born apparently normal and healthy, but develop
neurological symptoms (inertia, tremor, hind limb clasping, weight loss,
abnormal wide gait) at about 6 weeks of age. The health of the animals
subsequently declines leading to death at 10 weeks of age. Human males
carrying an MECP2 mutation are likewise severely affected and die within the
first two years of life. We are focussing on the Mecp2-null mouse in order
to try and understand what cellular processes are affected when MeCP2 is
absent. It is clear from our work and the work of others that the organ most
affected by MeCP2 deficiency is the brain and we have therefore been
analysing patterns of brain gene expression to see how these change. An
initial attempt to analyse differences in gene expression between normal
mice and Mecp2-null mice detected a few very subtle alterations, but we have
re-investigated this question using two methods: differential display and
microarray analysis.We have detected several genes that are inappropriately
expressed in the absence of MeCP2 and are optimistic that these findings
will shed light on the origins of human Rett syndrome.
Adrian Bird PhD, FRS, FRSE,
Buchanan Professor of Genetics, The Wellcome Trust Centre for Cell Biology,
University of Edinburgh, The King's Buildings, Edinburgh EH9 3JR.
September 2004
