Open AccessA Haplolethal Locus Uncovered by Deletions in the Mouse t Complex
Author(s) -
Victoria L. Browning,
Rebecca A. Bergstrom,
Sandra L Daigle,
John C. Schimenti
Publication year - 2002
Publication title -
genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.792
H-Index - 246
eISSN - 1943-2631
pISSN - 0016-6731
DOI - 10.1093/genetics/160.2.675
Subject(s) - biology , exencephaly , genetics , penetrance , phenotype , embryonic stem cell , gene dosage , locus (genetics) , aneuploidy , gene , genomic imprinting , haploinsufficiency , chromosome , gene expression , fetus , teratology , dna methylation , pregnancy
Proper levels of gene expression are important for normal mammalian development. Typically, altered gene dosage caused by karyotypic abnormalities results in embryonic lethality or birth defects. Segmental aneuploidy can be compatible with life but often results in contiguous gene syndromes. The ability to manipulate the mouse genome allows the systematic exploration of regions that are affected by alterations in gene dosage. To explore the effects of segmental haploidy in the mouse t complex on chromosome 17, radiation-induced deletion complexes centered at the Sod2 and D17Leh94 loci were generated in embryonic stem (ES) cells. A small interval was identified that, when hemizygous, caused specific embryonic lethal phenotypes (exencephaly and edema) in most fetuses. The penetrance of these phenotypes was background dependent. Additionally, evidence for parent-of-origin effects was observed. This genetic approach should be useful for identifying genes that are imprinted or whose dosage is critical for normal embryonic development.