Mouse models of aneuploidy to understand chromosome disorders

An organism or cell carrying a number of chromosomes that is not a multiple of the haploid count is in a state of aneuploidy. This condition results in significant changes in the level of expression of genes that are gained or lost from the aneuploid chromosome(s) and most cases in humans are not compatible with life. However, a few aneuploidies can lead to live births, typically associated with deleterious phenotypes. We do not understand why phenotypes arise from aneuploid syndromes in humans. Animal models have the potential to provide great insight, but less than a handful of mouse models of aneuploidy have been made, and no ideal system exists in which to study the effects of aneuploidy per se versus those of raised gene dosage. Here, we give an overview of human aneuploid syndromes, the effects on physiology of having an altered number of chromosomes and we present the currently available mouse models of aneuploidy, focusing on models of trisomy 21 (which causes Down syndrome) because this is the most common, and therefore, the most studied autosomal aneuploidy. Finally, we discuss the potential role of carrying an extra chromosome on aneuploid phenotypes, independent of changes in gene dosage, and methods by which this could be investigated further.

Automated summary

Aneuploidy refers to a state where an organism has a number of chromosomes that is not a multiple of the haploid count, which often leads to significant changes in gene expression levels and is usually incompatible with life in humans. While the mechanisms causing phenotypes from aneuploid syndromes are still not fully understood, animal models have the potential to provide insights. Down syndrome, caused by trisomy 21, is the most common autosomal aneuploidy and has been extensively studied.