The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression
Open accessAbstract
Mutations in the MECP2 gene cause Rett syndrome (RTT). Bdnf is a MeCP2 target gene; however, its role in RTT pathogenesis is unknown. We examined Bdnf conditional mutant mice for RTT-relevant pathologies and observed that loss of BDNF caused smaller brain size, smaller CA2 neurons, smaller glomerulus size, and a characteristic hindlimb-clasping phenotype. BDNF protein level was reduced in Mecp2 mutant mice, and deletion of Bdnf in Mecp2 mutants caused an earlier onset of RTT-like symptoms. To assess whether this interaction was functional and potentially therapeutically relevant, we increased BDNF expression in the Mecp2 mutant brain with a conditional Bdnf transgene. BDNF overexpression extended the lifespan, rescued a locomotor defect, and reversed an electrophysiological deficit observed in Mecp2 mutants. Our results provide in vivo evidence for a functional interaction between Mecp2 and Bdnf and demonstrate the physiological significance of altered BDNF expression/signaling in RTT disease progression.
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Mecp2−/y mice of the Bird strain have a slightly shorter lifespan than those of the Jaenisch line.
“This agrees closely with the findings of Guy and her colleagues (Guy et al., 2001), and thereby confirms that Mecp2−/y mice of the Bird strain have a slightly shorter lifespan than those of the Jaenisch line (Chang et al., 2006).”
From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Chang et al., 2006
The Results section compares survival of Mecp2 mutants with differing Bdnf levels, not survival of Bird-strain and Jaenisch-line Mecp2−/y mice. Searches for the strain names and a between-line lifespan comparison found no passage addressing the claimed difference. (LLM, conf=0.76)
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- Authors
- Chang, Q., Khare, G., Dani, V., Nelson, S., & Jaenisch, R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Massachusetts Institute of Technology (US)
- Brandeis University (US)
- Corresponding author
- Jaenisch, Rudolf
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 49
- Issue
- 3
- Pages
- 341-348
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2001657520
- Cited by
- 578
- References
- 4
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 24 · 2023: 19 · 2022: 23 · 2021: 31 · 2020: 23 · 2019: 25 · 2018: 18 · 2017: 23 · 2016: 25 · 2015: 39 · 2014: 38 · 2013: 39 · 2012: 48
- FWCI
- 20.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2759 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- International Rett Syndrome Foundation
- McKnight Foundation
- National Cancer Institute (RO1 CA087869)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- Rett syndrome, MeCP2, brain-derived neurotrophic factor, disease progression, conditional knockout mice, BDNF overexpression, lifespan extension, brain size
- MeSH terms
- Action Potentials, Animals, Animals, Newborn, Behavior, Animal, Brain, Disease Models, Animal, Electric Stimulation, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Immunohistochemistry, Male, Motor Activity, Mutation, Neurons, Organ Size, RNA, Messenger, Rett Syndrome, Mice, Knockout, Patch-Clamp Techniques, Disease Progression, Brain-Derived Neurotrophic Factor, Reverse Transcriptase Polymerase Chain Reaction, Mice, Methyl-CpG-Binding Protein 2, In Vitro Techniques
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