Nature Genetics
21, 390 - 395 (1999)
doi:10.1038/7720
Independent regulation of the two Pax5 alleles during B-cell development
Stephen L Nutt1, Susanne Vambrie1, Peter Steinlein1, Zbynek Kozmik3, Antonius Rolink2, Andreas Weith1
& Meinrad Busslinger11
Research Institute of Molecular Pathology,
Dr. Bohr-Gasse 7, A-1030 Vienna, Austria. 2
Basel Institute for Immunology,
Grenzacherstrasse487, CH-4005 Basel, Switzerland. 3
Institute of Molecular Genetics,
Flemingovo n.2, Prague, Czech Republic.
Correspondence should be addressed to Meinrad Busslinger Busslinger@nt.imp.univie.ac.atThe developmental control genes of the Pax family are frequently
associated with mouse mutants and human disease syndromes1,
2,
3.
The function of these transcription factors is sensitive to gene dosage, as
mutation of one allele1,
2,
3 or a modest increase in gene number4 results in phenotypic abnormalities. Pax5 has an important
role in B-cell and midbrain development5,
6,
7. By following
the expression of individual Pax5 alleles at the single-cell level,
we demonstrate here that Pax5 is subject to allele-specific regulation
during B-lymphopoiesis. Pax5 is predominantly transcribed from only
one allele in early progenitors and mature B cells, whereas it switches to
a biallelic transcription mode in immature B cells. The allele-specific regulation
of Pax5 is stochastic, reversible, independent of parental origin and
correlates with synchronous replication, in contrast with imprinted8,
9
and other monoallelically expressed genes10,
11. As a consequence,
B-lymphoid tissues are mosaics with respect to the transcribed Pax5
allele, and thus mutation of one allele in heterozygous mice results in deletion
of the cell population expressing the mutant allele due to loss of Pax5 function
at the single-cell level. Similar allele-specific regulation may be a common
mechanism causing the haploinsufficiency and frequent association of other
Pax genes with human disease.
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