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Cited by 50Down syndrome and intellectual disability researchCraniofacial Disorders and TreatmentsGenetics and Neurodevelopmental Disorders

Overlapping trisomies for human chromosome 21 orthologs produce similar effects on skull and brain morphology of Dp(16)1Yey and Ts65Dn mice

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Starbuck, John M., Dutka, Tara, Ratliff, Tabetha S., Reeves, Roger H., Richtsmeier, Joan T.·2014·American Journal of Medical Genetics Part A
DOI 10.1002/ajmg.a.36594PMC PMC4107150
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Abstract

Trisomy 21 results in gene‐dosage imbalance during embryogenesis and throughout life, ultimately causing multiple anomalies that contribute to the clinical manifestations of Down syndrome. Down syndrome is associated with manifestations of variable severity (e.g., heart anomalies, reduced growth, dental anomalies, shortened life‐span). Craniofacial dysmorphology and cognitive dysfunction are consistently observed in all people with Down syndrome. Mouse models are useful for studying the effects of gene‐dosage imbalance on development. We investigated quantitative changes in the skull and brain of the Dp(16)1Yey Down syndrome mouse model and compared these mice to Ts65Dn and Ts1Cje mouse models. Three‐dimensional micro‐computed tomography images of Dp(16)1Yey and euploid mouse crania were morphometrically evaluated. Cerebellar cross‐sectional area, Purkinje cell linear density, and granule cell density were evaluated relative to euploid littermates. Skulls of Dp(16)1Yey and Ts65Dn mice displayed similar changes in craniofacial morphology relative to their respective euploid littermates. Trisomy‐based differences in brain morphology were also similar in Dp(16)1Yey and Ts65Dn mice. These results validate examination of the genetic basis for craniofacial and brain phenotypes in Dp(16)1Yey mice and suggest that they, like Ts65Dn mice, are valuable tools for modeling the effects of trisomy 21 on development. © 2014 Wiley Periodicals, Inc.

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  • Dp16 mice exhibit hyperactive IFN signaling and recapitulate many phenotypes of DS including developmental delays, cranial malformations, and cognitive deficits.

    “Notably, Dp16 mice exhibit hyperactive IFN signaling and recapitulate many phenotypes of DS including developmental delays, cranial malformations, and cognitive deficits.38,40,42,43,44,45”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [43]

    The Discussion (page not provided) reports Down syndrome-like craniofacial abnormalities and cerebellar differences in Dp(16)1Yey mice. Our copy does not report hyperactive IFN signaling, developmental delays, or cognitive deficits in these mice; its mention of behavioral effects in the Introduction concerns Ts65Dn mice. (LLM, conf=0.90)

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Authors
Starbuck, J. M., Dutka, T., Ratliff, T. S., Reeves, R. H., & Richtsmeier, J. T.
Affiliations
  • Pennsylvania State University (US)
  • Johns Hopkins University (US)
Corresponding author
Richtsmeier, Joan T.
ORCID
Venue
American Journal of Medical Genetics Part A
Publisher
Wiley
Published
2014-05
Volume
164
Issue
8
Pages
1981-1990
ISSN
  • 1552-4825 (ISSN-L)
  • 1552-4833
DOI
10.1002/ajmg.a.36594
PMC
PMC4107150
OpenAlex
W2094062112
Cited by
50
References
2
Citations by year
2025: 4 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 3
FWCI
4.64
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • American Journal of Medical Genetics Part A (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Dental and Craniofacial Research (R01-HD038384, R01-DE022988)
  • National Institute of Health and Medical Research (R01-DE018500)
  • National Science Foundation (DGE-053135, BCS-1061563, BCS-0725227)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, Ts65Dn mouse model, craniofacial dysmorphism, skull morphology, brain structure, cerebellum, Purkinje cells, granule cells, gene dosage imbalance, mouse models of Down syndrome
MeSH terms
Animals, Brain, Cerebellum, Disease Models, Animal, Down Syndrome, Humans, Phenotype, Skull, Craniofacial Abnormalities, Mice

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