Asset Details
Do you wish to reserve the book?
Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy
Do you wish to request the book?
Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Loss of mouse C19orf12 homolog disturbs tubular ER homeostasis and leads to neuroaxonal dystrophy
2025
Overview
Neurodegeneration with brain iron accumulation (NBIA) is a group of rare diseases associated with genetic mutations in several genes including C19orf12. To explore the underlying mechanism of NBIA pathogenesis, we investigated a mouse homolog of human C19orf12 gene knockout mouse model. In the brains of knockout mice, an age-dependent accumulation of abundant axonal spheroids, alongside brain iron accumulation, neuroinflammation, α-synuclein and ubiquitin pathology was observed. Axonal spheroids were associated with abnormal ER and damaged mitochondria in knockout mice. These abnormal spheroids consistently contained the tubular ER protein reticulon 3 (RTN3) even at younger ages which preceded the onset of motor symptoms. The abnormal localized expansion of axonal ER underlies swollen axon terminals of dopaminergic neurons. The accumulated neuroaxonal swellings likely impair functioning of the dopaminergic system in the substantia nigra, striatum, and other brain regions, which ultimately led to motor function deficits in knockout mice. Altogether, the absence of C19orf12 in mouse brains recapitulates cardinal features of neuropathology in human NBIA, suggesting that C19orf12 is essential to maintain the tubular ER homeostasis in neuronal axon.
Publisher
BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
Subject
/ Analysis
/ Animals
/ Biomedical and Life Sciences
/ Brain
/ Endoplasmic Reticulum - metabolism
/ Endoplasmic Reticulum - pathology
/ Genes
/ Humans
/ Insects
/ Iron Metabolism Disorders - genetics
/ Iron Metabolism Disorders - metabolism
/ Iron Metabolism Disorders - pathology
/ Mice
/ Mitochondrial Proteins - genetics
/ MPAN
/ Mutation
/ Neuroaxonal Dystrophies - genetics
/ Neuroaxonal Dystrophies - metabolism
/ Neuroaxonal Dystrophies - pathology
/ Neurons
/ Proteins
