Axonal organization defects in the hippocampus of adult conditional BACE1 knockout mice
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Conditional loss of BACE1 in adult mouse brain results in abnormalities in the hippocampal mossy fiber pathway, which is important for learning and memory.
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BACE1fl/fl mice were previously generated and provided by R.V.
“BACE1fl/fl mice (C57BL/6-Bace1tm1.1mrl) were previously generated and provided by R.V. [36].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [36]
The Results section ('Generation and characterization of conditional BACE1 knockout mice'; page unavailable) states that BACE1fl/fl mice were generated, and Materials and Methods ('Animals'; page unavailable) describes how. R.V. is an author of the cited paper, but our copy does not say that he provided the mice to the citing researchers. (LLM, conf=0.83)
Experimental — accuracy not yet measuredTamoxifen administration between the ages of 4 and 8 weeks, after the majority of developmental myelination has taken place, avoids developmental and early postnatal effects of BACE1 knockout on myelin.
“To avoid developmental and early postnatal effects of BACE1 knockout on myelin [34], we used tamoxifen inducible Cre lines, with tamoxifen administered between the ages of 4 and 8 weeks (after the majority of developmental myelination has taken place [35]), according to standard protocols [36].”
From Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease (2024) · cites this paper as [36]
Conditional BACE1 deletion in neurons feature axon guidance defects.
“In addition, conditional BACE1 deletion in neurons feature axon guidance defects [644]”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [644]
Axon guidance abnormalities in the hippocampus persist in adult conditional BACE1 knockout, confirming an important role for BACE1 in adult circuitry architecture as well as developmental functions.
“Intriguingly, axon guidance abnormalities in the hippocampus persist in the adult conditional KO of BACE1, confirming an important role of the secretase in adult circuitry architecture as well as its established developmental functions (69,72–74).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [72]
BACE1 cleavage of CHL1 produces an intracellular membrane-bound C-terminal fragment that influences cytoskeleton dynamics and leads to growth cone collapse upon Sema3A.
“BACE1 cleavage yields an intracellular membrane-bound C-terminal fragment of CHL1 that is able to influence cytoskeleton dynamics, leading to growth cone collapse on presentation of the Sema3A cue.”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [72]
Conditional adult BACE1 knockout mitigates many side effects but axon guidance defects remain.
“Conditional BACE1 KO in adulthood mitigates many of these side effects but there remains impaired axon guidance defects (Ou-Yang et al., 2018).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Ou-Yang et al., 2018
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“1mrl) were previously generated and provided by R.V. [36].”
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BACE Inhibitor Clinical Trials for Alzheimer’s Disease
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Neuronal KCNQ2/3 channels are recruited to lipid raft microdomains by palmitoylation of BACE1
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Bace1 Deletion in the Adult Reverses Epileptiform Activity and Sleep–wake Disturbances in AD Mice
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- Authors
- Ou-Yang, M.-H., Kurz, J. E., Nomura, T., Popovic, J., Rajapaksha, T. W., Dong, H., Contractor, A., Chetkovich, D. M., Tourtellotte, W. G., & Vassar, R.
- Affiliations
- Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
- Northwestern University (US)
- Corresponding author
- Vassar, Robert
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2018-09-19
- Volume
- 10
- Issue
- 459
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC11017370
- OpenAlex
- W2892210142
- Cited by
- 94
- References
- 65
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 11 · 2023: 12 · 2022: 11 · 2021: 12 · 2020: 16 · 2019: 14 · 2018: 2
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AG022560, K02-NS046468, K26 OD010945)
- BrightFocus Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- BACE1, conditional knockout mice, hippocampus, mossy fiber pathway, dentate gyrus granule cells, CHL1, axon guidance, Alzheimer's disease, BACE1 inhibitors, adult neurogenesis, learning and memory
- MeSH terms
- Aging, Animals, Animals, Newborn, Axons, Cognition, Epilepsy, Hippocampus, Memory Disorders, Mice, Inbred C57BL, Myelin Sheath, Phenotype, Substrate Specificity, Aspartic Acid Endopeptidases, Apoptosis, Gene Deletion, Long-Term Potentiation, Mice, Knockout, Amyloid Precursor Protein Secretases, Neurogenesis
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