title: Mosaic analysis with double markers reveals cell-type-specific paternal growth dominance.
abstract: Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.
authors: Howard Hughes Medical Institute and Department of Biology, Stanford University, Stanford, CA 94305, USA. simon.hippenmeyer@ist.ac.at
authors: Simon
authors: S
authors: Hippenmeyer
authors: Randy L
authors: RL
authors: Johnson
authors: Liqun
authors: L
authors: Luo
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002875:Chromosomes / Q000235:genetics; D005799:Genes, Dominant; D005819:Genetic Markers; D018392:Genomic Imprinting; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009030:Mosaicism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D010641:Phenotype; D059010:Single-Cell Analysis; D024182:Uniparental Disomy / Q000235:genetics
chemical_list: D005819:Genetic Markers; C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II