Gene expression analysis of Fmr1-KO mouse caudate putamen reveals new preclinical biomarkers for fragile X syndrome
Year: 2026
Type: article
Abstract: Background Fragile X syndrome is a monogenic cause of autism spectrum disorder. Fmr1 -KO mice are a well-known model for the disease, and the model’s behavioral phenotype has been well-characterized. Unfortunately, translational molecular tissue biomarkers for this model remain sparse. Methods To identify new molecular biomarkers, we performed a gene sequencing analysis of caudate putamen tissue of Fmr1 -KO mice at the age of 7 weeks. RNA sequencing analysis revealed 13 genes to be upregulated and 37 genes to be downregulated in the caudate putamen of Fmr1 -KO mice. The two most upregulated genes were necdin ( Ndn ) and insulin degrading enzyme ( Ide ). Upregulation of Ndn and Ide genes was confirmed by real-time PCR. NDN protein expression was analyzed in the caudate putamen, hippocampus, and brainstem using immunofluorescent labeling. A co-labeling experiment assessed NDN expression in cholinergic neurons. Ide gene upregulation and its effect on insulin levels were evaluated, and protein expression analysis focused on NDN, parvalbumin, and myelin basic protein in the caudate putamen, cortex, and hippocampus. Results mRNA levels of Ndn and Ide and protein levels of NDN and IDE were strongly upregulated in the caudate putamen of Fmr1 -KO mice. NDN protein expression was also increased in the hippocampus and brainstem, with partial expression observed in cholinergic neurons. Upregulated Ide gene expression was associated with reduced insulin levels in Fmr1 -KO mice. Conclusion NDN and IDE emerge as promising candidates for preclinical disease-relevant biomarkers in Fmr1 -KO mice. Future research needs to demonstrate whether disease-modulating drugs can alter the expression profile of these proteins and ultimately alleviate disease symptoms.
Source: Frontiers in Neuroscience
Institution: University of Graz
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223357268