ArticleProceedings of the National Academy of Sciences of the United States of America2014
Transcriptome analysis of distinct mouse strains reveals kinesin light chain-1 splicing as an amyloid-β accumulation modifier.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Research progress of kinesin family in neurological diseases.Frontiers in cellular neuroscience · 2025Review
- The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.Nature human behaviour · 2024Article
- Unraveling the interplay of kinesin-1, tau, and microtubules in neurodegeneration associated with Alzheimer's disease.Frontiers in cellular neuroscience · 2024Review
- Molecular mechanism for kinesin-1 direct membrane recognition.Science advances · 2021Article
- Article
- Integrated analysis of human genetic association study and mouse transcriptome suggests LBH and SHF genes as novel susceptible genes for amyloid-β accumulation in Alzheimer's disease.Human genetics · 2018Article
- Practical considerations for choosing a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2017Review
- Article
- SKIP controls lysosome positioning using a composite kinesin-1 heavy and light chain-binding domain.Journal of cell science · 2017Article
- Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.PloS one · 2017Article
- A Unique Role for Endothelial Cell Kinesin Light Chain 1, Variant 1 in Leukocyte Transendothelial Migration.The American journal of pathology · 2016Article
- Toward more predictive genetic mouse models of Alzheimer's disease.Brain research bulletin · 2016Review
- The light chains of kinesin-1 are autoinhibited.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A new view of transcriptome complexity and regulation through the lens of local splicing variations.eLife · 2016Article
- Amyloid-β precursor protein: Multiple fragments, numerous transport routes and mechanisms.Experimental cell research · 2015Review
- Vaccinia virus protein complex F12/E2 interacts with kinesin light chain isoform 2 to engage the kinesin-1 motor complex.PLoS pathogens · 2015Article
- Kinesin light chain-1 variant E disrupts axonal transport and Aβ generation in Alzheimer's disease (comment on DOI 10.1002/bies.201400131).BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Article
- Article
- Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport.Molecular biology of the cell · 2014Article
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Authors and funding
27 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ). The genes that govern this process, however, have remained elusive. To this end, we combined distinct mouse strains with transcriptomics to directly identify disease-relevant genes. We show that AD model mice (APP-Tg) with DBA/2 genetic backgrounds have significantly lower levels of Aβ accumulation compared with SJL and C57BL/6 mice. We then applied brain transcriptomics to reveal the genes in DBA/2 that suppress Aβ accumulation. To avoid detecting secondarily affected genes by Aβ, we used non-Tg mice in the absence of Aβ pathology and selected candidate genes differently expressed in DBA/2 mice. Additional transcriptome analysis of APP-Tg mice with mixed genetic backgrounds revealed kinesin light chain-1 (Klc1) as an Aβ modifier, indicating a role for intracellular trafficking in Aβ accumulation. Aβ levels correlated with the expression levels of Klc1 splice variant E and the genotype of Klc1 in these APP-Tg mice. In humans, the expression levels of KLC1 variant E in brain and lymphocyte were significantly higher in AD patients compared with unaffected individuals. Finally, functional analysis using neuroblastoma cells showed that overexpression or knockdown of KLC1 variant E increases or decreases the production of Aβ, respectively. The identification of KLC1 variant E suggests that the dysfunction of intracellular trafficking is a causative factor of Aβ pathology. This unique combination of distinct mouse strains and model mice with transcriptomics is expected to be useful for the study of genetic mechanisms of other complex diseases.
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