Abstract
The retrotransposon long interspersed nuclear element-1 (LINE-1) can autonomously increase its copy number within a host genome through the retrotransposition process. LINE-1 is active in the germline and in neural progenitor cells, and its somatic retrotransposition activity has a broad impact on neural development and susceptibility to neuropsychiatric disorders. The method to quantify the genomic copy number of LINE-1 would be important in unraveling the role of retrotransposition, especially in the brain. However, because of the species-specific evolution of LINE-1 sequences, methods for quantifying the copy number should be independently developed. Here, we developed a quantitative PCR (qPCR) assay to measure the copy number of active LINE-1 subfamilies in mice. Using the assay, we investigated aging-associated alterations of LINE-1 copy number in several brain regions in wild-type mice and Polg+/D257A mice as a model for accelerated aging. We found that aged Polg+/D257A mice showed higher levels of the type GfII LINE-1 in the basal ganglia than the wild-type mice did, highlighting the importance of assays that focus on an individual active LINE-1 subfamily.
Highlights
Long interspersed nuclear element-1 (LINE-1) is a retrotransposon with a length of approximately 6 kb
We investigated aging-associated long interspersed nuclear element-1 (LINE-1) copy number change in Polg+/D257A mice, which we considered an animal model of chronic progressive external ophthalmoplegia (CPEO) that exhibits a premature aging characterized by accumulation of deleted mitochondrial DNA (mtDNA) and motor dysfunction (Fuke et al, 2014)
We found a subfamily-specific increase in the LINE-1 copy number in the basal ganglia of aged Polg+/D257A mice, showing the importance of a specific assay focusing on an individual member of the LINE-1 subfamilies
Summary
Long interspersed nuclear element-1 (LINE-1) is a retrotransposon with a length of approximately 6 kb. It occupies approximately 17 and 19% of the human genome and mouse genome, respectively (Lander et al, 2001; Mouse Genome Sequencing Consortium et al, 2002). In addition to germline cells, recent findings suggest that LINE-1 is active in neural precursor cells during early neurodevelopment and adult neurogenesis in the hippocampus, resulting in somatic mosaicism in brain cells (Erwin et al, 2014; Evrony et al, 2016; Faulkner and Billon, 2018; Saleh et al, 2019). Somatic LINE-1 retrotransposition in neurons is considered to be involved in the pathophysiology of neuropsychiatric disorders (Muotri et al, 2010; Coufal et al, 2011; Bundo et al, 2014; Iwamoto, 2019; Saleh et al, 2019)
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