Aljuraysi, Sultan, Platt, Mark, Pulix, Michela, Poptani, Harish 
ORCID: 0000-0002-0593-3235 and Plagge, Antonius ORCID: 0000-0001-6592-1343
(2024)
Microcephaly with a disproportionate hippocampal reduction, stem cell loss and neuronal lipid droplet symptoms in Trappc9 KO mice
Neurobiology of Disease, 192.
p. 106431.
ISSN 0969-9961, 1095-953X
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Aljuraysi S NeurobiolDis 24 Trappc9 KO.pdf - Open Access published version Download (8MB) | Preview |
Abstract
Mutations of the human TRAFFICKING PROTEIN PARTICLE COMPLEX SUBUNIT 9 (TRAPPC9) cause a neurodevelopmental disorder characterised by microcephaly and intellectual disability. Trappc9 constitutes a subunit specific to the intracellular membrane-associated TrappII complex. The TrappII complex interacts with Rab11 and Rab18, the latter being specifically associated with lipid droplets (LDs). Here we used non-invasive imaging to characterise Trappc9 knock-out (KO) mice as a model of the human hereditary disorder. KOs developed postnatal microcephaly with many grey and white matter regions being affected. In vivo magnetic resonance imaging (MRI) identified a disproportionately stronger volume reduction in the hippocampus, which was associated with a significant loss of Sox2-positive neural stem and progenitor cells. Diffusion tensor imaging indicated a reduced organisation or integrity of white matter areas. Trappc9 KOs displayed behavioural abnormalities in several tests related to exploration, learning and memory. Trappc9-deficient primary hippocampal neurons accumulated a larger LD volume per cell following Oleic Acid stimulation, and the coating of LDs by Perilipin-2 was much reduced. Additionally, Trappc9 KOs developed obesity, which was significantly more severe in females than in males. Our findings indicate that, beyond previously reported Rab11-related vesicle transport defects, dysfunctions in LD homeostasis might contribute to the neurobiological symptoms of Trappc9 deficiency.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TrappII, Trappc9, Microcephaly, Intellectual disability, Hippocampus, Neural progenitor cell, Lipid droplet, Obesity, Magnetic resonance imaging |
| Divisions: | Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 16 Feb 2024 08:23 |
| Last Modified: | 28 Feb 2026 14:33 |
| DOI: | 10.1016/j.nbd.2024.106431 |
| Related Websites: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178676 |
| Disclaimer: | The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate. |
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