Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death

• Published in: PloS one 2012-08, Vol.7 (8), p.e43356-e43356
• Main Authors: Vatin, Magalie, Burgio, Gaetan, Renault, Gilles, Laissue, Paul, Firlej, Virginie, Mondon, Françoise, Montagutelli, Xavier, Vaiman, Daniel, Serres, Catherine, Ziyyat, Ahmed
• Format: Article
• Language: English
• Subjects: Animals; Biology; Cartography; Cell growth; Chromosome 1; Chromosomes, Mammalian; Chromosomes, Mammalian - genetics; Deregulation; Embryo Loss; Embryo Loss - etiology; Embryo Loss - genetics; Embryogenesis; Etiology; Female; Gene mapping; Genes; Genetic analysis; Genetic research; Genetics; Genomes; Genomics; Genotype; Genotypes; Growth factors; Infertility; Interspecific; Kinases; Lethality; Life Sciences; Mammals; Medicine; Mice; Microsatellite Repeats; Microsatellite Repeats - genetics; Miscarriage; Mus spretus; Mutation; Phenotypes; Pregnancy; Proteasomes; Quantitative genetics; Quantitative Trait Loci; Quantitative Trait Loci - genetics; Reverse Transcriptase Polymerase Chain Reaction; Signaling; Stem cells; TOR protein; Transplants & implants; Ultrasonic imaging; Uterus; Vascular endothelial growth factor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0043356

Recurrent spontaneous abortion (RSA) is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS) in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (∼30%). Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.