The initiation of X-chromosome inactivation in female mammals is contr
olled by a key locus, the X-inactivation centre (Xic). The Xist gene,
which maps to the candidate region for Xic and is expressed exclusivel
y from the inactive X chromosome, is thought to be an essential compon
ent of the Xic, To test whether sequences spanning several hundred kil
obases and including Xist from the Xic region are capable of initiatin
g inactivation, we have created a series of transgenic mice using a 46
0 kb yeast artificial chromosome (YAC). Analysis in these mice of the
expression of Xist, of a LacZ reporter gene and of two genes in the re
gion that are normally silent on the inactive X chromosome, suggests t
hat essential sequences for Xist expression and X-inactivation may be
absent in these transgenic animals.