| First Author | Liang ZS | Year | 2020 |
| Journal | PLoS Genet | Volume | 16 |
| Issue | 9 | Pages | e1008916 |
| PubMed ID | 32877400 | Mgi Jnum | J:294716 |
| Mgi Id | MGI:6456643 | Doi | 10.1371/journal.pgen.1008916 |
| Citation | Liang ZS, et al. (2020) Trappc9 deficiency causes parent-of-origin dependent microcephaly and obesity. PLoS Genet 16(9):e1008916 |
| abstractText | Some imprinted genes exhibit parental origin specific expression bias rather than being transcribed exclusively from one copy. The physiological relevance of this remains poorly understood. In an analysis of brain-specific allele-biased expression, we identified that Trappc9, a cellular trafficking factor, was expressed predominantly (~70%) from the maternally inherited allele. Loss-of-function mutations in human TRAPPC9 cause a rare neurodevelopmental syndrome characterized by microcephaly and obesity. By studying Trappc9 null mice we discovered that homozygous mutant mice showed a reduction in brain size, exploratory activity and social memory, as well as a marked increase in body weight. A role for Trappc9 in energy balance was further supported by increased ad libitum food intake in a child with TRAPPC9 deficiency. Strikingly, heterozygous mice lacking the maternal allele (70% reduced expression) had pathology similar to homozygous mutants, whereas mice lacking the paternal allele (30% reduction) were phenotypically normal. Taken together, we conclude that Trappc9 deficient mice recapitulate key pathological features of TRAPPC9 mutations in humans and identify a role for Trappc9 and its imprinting in controlling brain development and metabolism. |
