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Cited by 28Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersAutism Spectrum Disorder Research

In tribute to Bob Blanchard: Divergent behavioral phenotypes of 16p11.2 deletion mice reared in same-genotype versus mixed-genotype cages

Yang, Mu, Lewis, Freeman, Foley, Gillian, Crawley, Jacqueline N.·2015·Physiology & Behavior
DOI 10.1016/j.physbeh.2015.04.023
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Abstract

Mouse models offer indispensable heuristic tools for studying genetic and environmental causes of neuropsychiatric disorders, including autism. Development of useful animal models of complex human behaviors depends not only on extensive knowledge of the human disease, but also on a deep understanding of animal behavior and ethology. Robert and Caroline Blanchard pioneered a number of elegant social paradigms in rodents. Their early work led to systematic delineations of rodent naturalist defensive behaviors,which were proven to be highly useful models of human psychiatric disorders, including fear and anxiety. Their work using the Visible Burrow System to study social stress in rats represented an unprecedented approach to study biological mechanisms of depression. In recent years, their extensive knowledge of mouse behavior and ethology enabled them to quickly become leading figures in the field of behavioral genetics of autism. To commemorate Robert Blanchard's influences on animal models of human psychiatric disorders, here we describe a study conceptualized and led by Mu Yang who was trained as a graduate student in the Blanchard laboratory in the early 2000s. This investigation focuses on social housing in a genetic mouse model of 16p11.2 deletion syndrome. Heterozygous deletions and duplications of a segment containing about 29 genes on human chromosome 16 appear in approximately 0.5–1% of all cases of autism. 16p11.2 deletion syndrome is also associated with intellectual disabilities and speech impairments. Our previous studies showed that a mouse model of 16p11.2 deletion syndrome exhibited deficits in vocalizations and novel object recognition, as compared to wildtype littermate control cagemates. In the spirit of Bob Blanchard's careful attention to the role of social dominance in rodent behaviors, we became interested in the question of whether behavioral outcomes of a mutation differ when mutants are housed in mixed genotype cages, versus housing only mutants together in one group cage, and only wildtype littermates together in another group cage after weaning. 16p11.2 deletion presented a particularly good model organism to investigate this question, because the heterozygotes are smaller than their wildtype littermates, and may therefore become subordinate to their larger cagemates.Wildtype and heterozygotes were housed with cagemates of the same genotype (same-genotype cage) or with cagemates of the opposite genotype (mixed-genotype cage). Current results replicated social vocalization and object recognition deficits that we previously found in heterozygotes living in mixed-genotype cages. In contrast, heterozygotes that lived in same-genotype cages emitted normal numbers of vocalizations during male–female interactions, and displayed normal novel object recognition, indicating that the deletion per se was not sufficient to cause cognitive or social deficits. Social approach, same-sex social interaction, anxiety-related behavior, depression-related behavior, and open field exploration were not different between genotypes, and were not affected by housing in mixed versus in same-genotype cages. These findings suggest that elements of the home cage social environment could interact with genotype to impact aspects of disease phenotypes. Current findings are discussed as potentially reflecting behavioral deficits resulted from social stress, as inspired by a seminal paper by Bob and Caroline Blanchard [1].

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  • All three lines of 16p11.2+/− mice display social deficits in various testing paradigms and an array of cognitive deficits.

    “All 3 lines of 16p11.2+/− mice display social deficits in various testing paradigms [59–64], and an array of cognitive deficits [4, 59, 62–68].”

    From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [63]

  • Hyperlocomotion is broadly reported in 16p11.2+/− mice, another behavioral feature that does not coincide directly with human symptomology.

    “Hyperlocomotion is also broadly reported in 16p11.2+/− mice [4, 5, 59, 61, 63, 64, 70], another behavioral feature that does not coincide directly with human symptomology.”

    From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [63]

  • 16p11.2+/− models show reduced body size/weight, in contrast to the human obesity phenotype.

    “However, 16p11.2+/− models show reduced body size/weight [4, 5, 60, 61, 63], in contrast to the human obesity phenotype.”

    From 16p11.2 Copy Number Variations and Neurodevelopmental Disorders (2020) · cites this paper as [63]

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Authors
Yang, M., Lewis, F., Foley, G., & Crawley, J. N.
Affiliations
University of California Davis Medical Center (US)
Corresponding author
Yang, Mu
ORCID
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2015-07
Volume
146
Pages
16-27
ISSN
0031-9384 (ISSN-L)
DOI
10.1016/j.physbeh.2015.04.023
OpenAlex
W776910720
Cited by
28
References
107
Citations by year
2026: 1 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 1 · 2015: 1
FWCI
2.05
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Physiology & Behavior (publishedVersion)
  • PubMed (publishedVersion)
Funders
Simons Foundation (##204340)
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 › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
16p11.2 deletion syndrome, mouse models of autism, social housing, social dominance, social vocalizations, novel object recognition, behavioral phenotypes, heterozygotes, social stress, depression, genetic and environmental factors, intellectual disability, speech disorders
MeSH terms
Adaptation, Ocular, Animals, Behavior, Animal, Mental Disorders, Chromosome Deletion, Chromosomes, Human, Pair 16, Disease Models, Animal, Exploratory Behavior, Female, Genotype, Humans, Interpersonal Relations, Luminescent Proteins, Male, Mice, Transgenic, Phenotype, Vocalization, Animal, Maze Learning, Recognition, Psychology, Mice

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