Bibliographic Details
| Title: |
Hyperphenylalaninemia and serotonin deficiency in Dnajc12-deficient mice |
| Authors: |
Yunqing Cao, Oliver Popp, Niccolo Milani, Fatimunnisa Qadri, Ralf Kühn, Philipp Mertins, Michael Bader, Natalia Alenina |
| Source: |
Communications Biology, Vol 7, Iss 1, Pp 1-12 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
Biology (General), QH301-705.5 |
| More Details: |
Abstract Serotonin exerts numerous neurological and physiological actions in the brain and in the periphery. It is generated by two different tryptophan hydroxylase enzymes, TPH1 and TPH2, in the periphery and in the brain, respectively, which are members of the aromatic amino acid hydroxylase (AAAH) family together with phenylalanine hydroxylase (PAH), degrading phenylalanine, and tyrosine hydroxylase (TH), generating dopamine. In this study, we show that the co-chaperone DNAJC12 is downregulated in serotonergic neurons in the brain of mice lacking TPH2 and thereby central serotonin. DNAJC12 has been described to regulate the stability of PAH and mutations in its gene cause hyperphenylalaninemia and neurological symptoms in patients. We show that DNAJC12 also binds and stabilizes TPH1 and TPH2 in transfected cells. In order to clarify the importance of DNAJC12 in the regulation of neurotransmitter synthesis and phenylalanine degradation in vivo, we generated DNAJC12-deficient mice. These mice show reduced levels and activity of PAH, TPH2, and TPH1 in liver, brain, and pineal gland, respectively, and experience hyperphenylalaninemia and central and peripheral serotonin deficiency. These data support a pivotal role of DNAJC12 in the regulation of AAAH and thereby in neurotransmitter synthesis and phenylalanine homeostasis. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2399-3642 |
| Relation: |
https://doaj.org/toc/2399-3642 |
| DOI: |
10.1038/s42003-024-07360-6 |
| Access URL: |
https://doaj.org/article/a7fb70239ef94afdb70f3b52914da792 |
| Accession Number: |
edsdoj.7fb70239ef94afdb70f3b52914da792 |
| Database: |
Directory of Open Access Journals |
