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

Kristina Aldridge, Roger H. Reeves, Lisa E. Olson, Joan Therese Richtsmeier

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1060-1070
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume143
Issue number10
DOIs
StatePublished - May 15 2007

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Trisomy
Aneuploidy
Down Syndrome
Cerebellum
Brain
Genes
Chromosomes, Human, Pair 21
Gene Dosage
Genetic Models
Human Chromosomes
Chromosomes
Phenotype

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)

Cite this

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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.",
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Differential effects of trisomy on brain shape and volume in related aneuploid mouse models. / Aldridge, Kristina; Reeves, Roger H.; Olson, Lisa E.; Richtsmeier, Joan Therese.

In: American Journal of Medical Genetics, Part A, Vol. 143, No. 10, 15.05.2007, p. 1060-1070.

Research output: Contribution to journalArticle

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