Analysis of Brain, Blood, and Testis Phenotypes Lacking the Vps13a Gene in C57BL/6N Mice.
Jitrapa PinyomahakulMasataka IseMeiko KawamuraTakashi YamadaKentaro OkuyamaShinsuke ShibataJun TakizawaManabu AbeKenji SakimuraHirohide TakebayashiPublished in: International journal of molecular sciences (2024)
The Vps13a gene encodes a lipid transfer protein called VPS13A, or chorein, associated with mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs), mitochondria-endosomes, and lipid droplets. This protein plays a crucial role in inter-organelle communication and lipid transport. Mutations in the VPS13A gene are implicated in the pathogenesis of chorea-acanthocytosis (ChAc), a rare autosomal recessive neurodegenerative disorder characterized by chorea, orofacial dyskinesias, hyperkinetic movements, seizures, cognitive impairment, and acanthocytosis. Previous mouse models of ChAc have shown variable disease phenotypes depending on the genetic background. In this study, we report the generation of a Vps13a flox allele in a pure C57BL/6N mouse background and the subsequent creation of Vps13a knockout (KO) mice via Cre-recombination. Our Vps13a KO mice exhibited increased reticulocytes but not acanthocytes in peripheral blood smears. Additionally, there were no significant differences in the GFAP- and Iba1-positive cells in the striatum, the basal ganglia of the central nervous system. Interestingly, we observed abnormal spermatogenesis leading to male infertility. These findings indicate that Vps13a KO mice are valuable models for studying male infertility and some hematological aspects of ChAc.
Keyphrases
- endoplasmic reticulum
- high fat diet induced
- genome wide
- copy number
- cognitive impairment
- peripheral blood
- induced apoptosis
- fatty acid
- cell death
- gene expression
- mouse model
- wild type
- type diabetes
- metabolic syndrome
- genome wide identification
- dna methylation
- protein protein
- small molecule
- adipose tissue
- cell cycle arrest
- reactive oxygen species
- white matter
- transcription factor
- polycystic ovary syndrome
- dna repair
- brain injury
- signaling pathway