Influence of paternally imprinted genes on development.
The parental origin of chromosomes is critical for normal development in the mouse because some genes are imprinted resulting in a predetermined preferential expression of one of the alleles. Duplication of the paternal (AG: androgenones) or maternal (GG/PG: gynogenones/parthenogenones) genomes will result in an excess or deficiency of gene dosage with corresponding phenotypic effects. Here, we report on the effects of paternally imprinted genes on development following introduction of the AG inner cell mass into normal blastocysts. There was a striking increase in embryonic growth by up to 50%, and a characteristic change in embryonic shape, partly because of the corresponding increase in length of the anterior-posterior axis. These changes, between e12-e15, were proportional to the contribution from AG cells to the embryo. However, a contribution of AG cells in excess of 50% was invariably lethal as development progressed to e15. A limited number of chimeras were capable of full-term development provided there was a relatively low contribution from AG cells. The distribution of AG cells in chimeras was not uniform, especially later in development when there was a disproportionate presence of AG cells in the mesodermally derived tissues. Their contribution was consistently greater in the heart and skeletal muscle, but was considerably lower in the brain. Chimeras detected after birth were either dead or developed severe abnormalities of the skeletal elements, particularly of the ribs which were enlarged, distorted and fused, with greatly increased cartilaginous material with an absence of normal ossification. These phenotypic effects in chimeras are reciprocal to those observed in the presence of GG/PG cells, which resulted in a substantial size reduction approaching 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Barton
S C
SC
Department of Molecular Embryology, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
Ferguson-Smith
A C
AC
Fundele
R
R
Surani
M A
MA
D000818:Animals; D001755:Blastocyst; D001842:Bone and Bones / Q000196:embryology; D002678:Chimera / Q000235:genetics*; D005818:Genetic Engineering / Q000379:methods; D016678:Genome; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics; D008845:Microinjections; D010641:Phenotype