Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2)
Abstract
Contiguous gene syndromes (CGS) refer to a group of disorders associated with chromosomal rearrangements in which the phenotype is thought to result from altered copy number of physically linked dosage-sensitive genes. Smith-Magenis syndrome and [dup(17)(p11.2p11.2)] are CGS associated with a heterozygous deletion or duplication of band p11.2 of chromosome 17, respectively. We previously constructed animal models for these CGSs by engineering rearranged chromosomes carrying a deletion/deficiency [Df(11)17] (Del mutant) or a duplication [Dp(11)17 ] (Dup mutant) of the syntenic region on mouse chromosome 11. Here we present a behavioral analysis of these models indicating that heterozygous male mice carrying the engineered deletion or the duplication are hypoactive or hyperactive, respectively. In addition, male Dup mutant mice, but not Del mutant mice, have impaired contextual fear conditioning. Circadian rhythm studies revealed period length differences in Del mutant mice, but not Dup mutant mice. These results indicate that some of the behavioral abnormalities are gene dosage sensitive, whereas other behavioral abnormalities are specific to mice carrying the deletion or the duplication and can be observed in a sex preferential manner. Our findings suggest that there is a gene(s) present in this defined genomic interval that is responsible for behavioral abnormalities in the mouse, as has been shown for the human syntenic region.
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Mice with a heterozygous deletion of Rai1 display a shortened locomotor activity period, although these mice are of mixed genetic background containing C57BL/6, which do not produce pineal melatonin.
“Mice with a heterozygous deletion of Rai1 display a shortened locomotor activity period133,134, although these mice are of mixed genetic background containing C57BL/6, which do not produce pineal melatonin.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [133]
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- Authors
- Walz, K.
- Affiliations
- Baylor College of Medicine (US)
- Corresponding author
- Walz, K.
- ORCID
- Walz, K.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-12-17
- Volume
- 13
- Issue
- 4
- Pages
- 367-378
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2165675397
- Cited by
- 74
- References
- 26
- Citations by year
- 2025: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 3 · 2015: 2 · 2014: 4 · 2013: 8 · 2012: 6
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01ca075719-05)
- National Cancer Institute (P01CA75719)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Williams Syndrome Research
- Keywords
- Smith-Magenis syndrome, contiguous gene syndrome, gene dosage sensitivity, mouse model, behavioral phenotypes, hypoactivity, hyperactivity, contextual fear conditioning, circadian rhythm, period length, sex differences
- MeSH terms
- Animals, Mental Disorders, Chromosomes, Human, Pair 17, Disease Models, Animal, Female, Humans, Male, Mice, Inbred C57BL, Models, Genetic, Syndrome, Gene Deletion, Gene Duplication, Chromosome Disorders, Mice
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