Dysregulation of locus coeruleus development in congenital central hypoventilation syndrome.
- Nobuta, Hiroko;
- Cilio, Maria Roberta;
- Danhaive, Olivier;
- Tsai, Hui-Hsin;
- Tupal, Srinivasan;
- Chang, Sandra M;
- Murnen, Alice;
- Kreitzer, Faith;
- Bravo, Verenice;
- Czeisler, Catherine;
- Gokozan, Hamza Numan;
- Gygli, Patrick;
- Bush, Sean;
- Weese-Mayer, Debra E;
- Conklin, Bruce;
- Yee, Siu-Pok;
- Huang, Eric J;
- Gray, Paul A;
- Rowitch, David;
- Otero, José Javier
- et al.
Published Web Location
https://doi.org/10.1007/s00401-015-1441-0Abstract
Human congenital central hypoventilation syndrome (CCHS), resulting from mutations in transcription factor PHOX2B, manifests with impaired responses to hypoxemia and hypercapnia especially during sleep. To identify brainstem structures developmentally affected in CCHS, we analyzed two postmortem neonatal-lethal cases with confirmed polyalanine repeat expansion (PARM) or Non-PARM (PHOX2B∆8) mutation of PHOX2B. Both human cases showed neuronal losses within the locus coeruleus (LC), which is important for central noradrenergic signaling. Using a conditionally active transgenic mouse model of the PHOX2B∆8 mutation, we found that early embryonic expression (
Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.