Deletion of Mecp2 in Sim1-Expressing Neurons Reveals a Critical Role for MeCP2 in Feeding Behavior, Aggression, and the Response to Stress
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Rett Syndrome (RTT) is an autism spectrum disorder caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). In order to map the neuroanatomic origins of the complex neuropsychiatric behaviors observed in patients with RTT and to uncover endogenous functions of MeCP2 in the hypothalamus, we removed Mecp2 from Sim1-expressing neurons in the hypothalamus using Cre-loxP technology. Loss of MeCP2 in Sim1-expressing neurons resulted in mice that recapitulated the abnormal physiological stress response that is seen upon MeCP2 dysfunction in the entire brain. Surprisingly, we also uncovered a role for MeCP2 in the regulation of social and feeding behaviors since the Mecp2 conditional knockout (CKO) mice were aggressive, hyperphagic, and obese. This study demonstrates that deleting Mecp2 in a defined brain region is an excellent approach to map the neuronal origins of complex behaviors and provides new insight about the function of MeCP2 in specific neurons.
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Conditional mutation of Mecp2 by a Sim1-cre results in a subset of Mecp2 null symptoms that affect metabolism through the dysregulation of neuroendocrine pathways.
“conditional mutation of Mecp2 by a Sim1-cre results in a subset of Mecp2 null symptoms that affect metabolism through the dysregulation of neuroendocrine pathways51.”
From A suppressor screen in Mecp2 mutant mice implicates cholesterol metabolism in Rett syndrome (2013) · cites this paper as [51]
Mecp2 knockout mice show increased aggression.
“Mecp2 KO mice also show increased aggression [20].”
From An integrated analysis of genes and functional pathways for aggression in human and rodent models (2019) · cites this paper as [20]
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- Authors
- Fyffe, S. L., Neul, J. L., Samaco, R. C., Chao, H.-T., Ben-Shachar, S., Moretti, P., McGill, B. E., Goulding, E. H., Sullivan, E., Tecott, L. H., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zoghbi, Huda Y.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 59
- Issue
- 6
- Pages
- 947-958
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2597031
- OpenAlex
- W1992789817
- Cited by
- 254
- References
- 62
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 12 · 2020: 9 · 2019: 13 · 2018: 11 · 2017: 11 · 2016: 19 · 2015: 21 · 2014: 26 · 2013: 19 · 2012: 23
- FWCI
- 9.12
- 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, 1780 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)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- International Rett Syndrome Foundation
- National Institute of Neurological Disorders and Stroke (NS057819)
- National Institutes of Health
- Autism Speaks
- Simons Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- MeCP2, Rett syndrome, hypothalamus, conditional knockout mice, feeding behavior, hyperphagia, obesity, aggression, stress response, social behavior
- MeSH terms
- Adaptation, Psychological, Aggression, Animals, Appetite Regulation, Feeding Behavior, Genetic Engineering, Hypothalamus, Mice, Inbred Strains, Neurons, Repressor Proteins, Social Behavior, Stress, Psychological, Gene Deletion, Mice, Knockout, Adiposity, Mice, Methyl-CpG-Binding Protein 2, Basic Helix-Loop-Helix Proteins
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