Aljuraysi, Sultan, Platt, Mark, Pulix, Michela, Poptani, Harish 
ORCID: 0000-0002-0593-3235 and Plagge, Antonius ORCID: 0000-0001-6592-1343
(2023)
Microcephaly with a disproportionate hippocampal reduction, stem cell loss and neuronal lipid droplet symptoms in<i>Trappc9</i>KO mice.
[Preprint]
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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 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: | Preprint |
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| Uncontrolled Keywords: | Neurosciences, Biomedical Imaging, Brain Disorders, Intellectual and Developmental Disabilities (IDD), Stem Cell Research - Nonembryonic - Non-Human, Stem Cell Research, Mental Health, 2.1 Biological and endogenous factors, 2 Aetiology, Neurological |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 21 Nov 2023 11:53 |
| Last Modified: | 23 Mar 2024 04:01 |
| DOI: | 10.1101/2023.11.20.567859 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3176932 |
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