The developmental control genes of the Pax family are frequently associated
with mouse mutants and human disease syndromes(1-3). The function of these
transcription factors is sensitive to gene dosage, as mutation of one alle
le(1-3) or a modest increase in gene number(4) results in phenotypic abnorm
alities. Pax5 has an important role in B-cell and midbrain development(5-7)
. By following the expression of individual Pax5 alleles at the single-cell
level, we demonstrate here that Pax5 is subject to allele-specific regulat
ion during B-lymphopoiesis. Pax5 is predominantly transcribed from only one
allele in early progenitors and mature B cells, whereas it switches to a b
iallelic transcription mode in immature B cells. The allele-specific regula
tion of Pax5 is stochastic, reversible, independent of parental origin and
correlates with synchronous replication, in contrast with imprinted(8,9) an
d other monoallelically expressed genes(10,11). As a consequence, B-lymphoi
d tissues are mosaics with respect to the transcribed Pax5 allele, and thus
mutation of one allele in heterozygous mice results in deletion of the cel
l population expressing the mutant allele due to loss of Pax5 function at t
he single-cell level. Similar allele-specific regulation may be a common me
chanism causing the haploinsufficiency and frequent association of other Pa
x genes with human disease.