Differential effects of trisomy on brain shape and volume in related aneuploid mouse models

Authors

  • Kristina Aldridge,

    1. Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania
    Current affiliation:
    1. Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212.
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  • Roger H. Reeves,

    1. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Lisa E. Olson,

    1. Department of Biology, University of Redlands, Redlands, California
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  • Joan T. Richtsmeier

    Corresponding author
    1. Department of Anthropology, The Pennsylvania State University, University Park, Pennsylvania
    2. Center for Craniofacial Development and Disorders, The Johns Hopkins Hospital, Baltimore, Maryland
    • Department of Anthropology, The Pennsylvania State University, University Park, 409 Carpenter Bldg, PA 16801.
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  • How to cite this article: Aldridge K, Reeves RH, Olson LE, Richtsmeier JT. 2007. Differential effects of trisomy on brain shape and volume in related aneuploid mouse models. Am J Med Genet Part A 143A:1060–1070.

Abstract

Down syndrome (DS) results from inheritance of three copies of human chromosome 21 (Hsa21). Individuals with DS have a significantly smaller brain size overall and a disproportionately small cerebellum. The small cerebellum is seen in Ts65Dn mice, which have segmental trisomy for orthologs of about half the genes on Hsa21 and provide a genetic model for DS. While small cerebellar size is well-established in mouse and humans, much less is known about the shape of the brain in trisomy. Here we conduct a morphometric analysis of the whole brain and cerebellum in Ts65Dn mice and show that the differences with euploid littermates are largely a function of volume and not of shape. This is not the case in two aneuploid mouse models that have fewer genes orthologous to Hsa21 than Ts65Dn. Ts1Rhr is trisomic for genes corresponding to the so-called Down syndrome critical region (DSCR), which was purported to contain a dosage sensitive gene or genes responsible for many phenotypes of DS. Ms1Rhr is monosomic for the same segment. These models show effects on cerebellum and overall brain that are different from each other and from Ts65Dn. These models can help to identify the contributions of genes from different regions of the chromosome on this and other aspects of brain development in trisomy. © 2007 Wiley-Liss, Inc.

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