Holtzman D M, Bayney R M, Li Y W, Khosrovi H, Berger C N, Epstein C J, Mobley W C
Department of Neurology, University of California, San Francisco 94143.
EMBO J. 1992 Feb;11(2):619-27. doi: 10.1002/j.1460-2075.1992.tb05094.x.
In humans, trisomy 21 results in a specific phenotype known as Down syndrome (DS). The mechanism by which an extra copy of normal genes leads to the DS phenotype is unknown. Most studies in DS and other aneuploid organisms have shown that gene dose is proportional to gene expression. To date, most genes examined have encoded either metabolic enzymes or constitutively expressed products. In the trisomy 16 mouse, an animal model of DS, we found marked dysregulation of two developmentally regulated genes, App and Prn-p. Dysregulation varied from tissue to tissue and during development in the same tissue. We conclude that abnormal phenotypes seen in aneuploid conditions may result in part from disordered expression of developmentally regulated genes.
在人类中，21三体导致一种称为唐氏综合征（DS）的特定表型。正常基因的额外拷贝导致DS表型的机制尚不清楚。大多数关于DS和其他非整倍体生物的研究表明，基因剂量与基因表达成正比。迄今为止，大多数检测的基因编码的要么是代谢酶，要么是组成型表达产物。在16三体小鼠（一种DS动物模型）中，我们发现两个发育调控基因App和Prn-p存在明显的表达失调。这种失调在不同组织之间以及同一组织的发育过程中都有所不同。我们得出结论，非整倍体条件下出现的异常表型可能部分是由于发育调控基因的表达紊乱所致。
