Deletion of the App-Runx1 region in mice models human partial monosomy 21

• DOI: 10.1242/dmm.017814
• Publication Date: 2015-04-17T01:22:54Z
• Authors: Thomas Arbogast; Matthieu Raveau; Claire Chevalier; Valérie Nalesso; Doulaye Dembele; Hugues Jacobs; Olivia Wendling; Michel Roux; Arnaud Duchon; Yann Herault
• Keywords: Monosomy; RUNX1

Partial monosomy 21 (PM21) is a rare chromosomal abnormality that characterized by the loss of variable segment along human chromosome (Hsa21). The clinical phenotypes this are heterogeneous and range from mild alterations to lethal consequences, depending on affected region Hsa21. most common features include intellectual disabilities, craniofacial dysmorphology, short stature, muscular cardiac defects. As complement genetic approaches, our team has developed new monosomic mouse models carry deletions Hsa21 syntenic regions in order identify dosage-sensitive genes responsible for symptoms. We focus here Ms5Yah model, which 7.7-Mb been deleted App Runx1 genes. mice display high postnatal lethality, with few surviving individuals showing growth retardation, motor coordination deficits, spatial learning memory impairments. Further studies confirmed gene dosage effect hippocampus, pinpointed disruptions pathways related cell adhesion (involving App, Cntnap5b, Lgals3bp, Mag, Mcam, Npnt, Pcdhb2, Pcdhb3, Pcdhb4, Pcdhb6, Pcdhb7, Pcdhb8, Pcdhb16 Vwf). Our PM21 model first morphological abnormalities behavioural similar those found humans, it therefore demonstrates major contribution App-Runx1 pathophysiology PM21.