Widespread impairment of cell proliferation in the neonate Ts65Dn mouse, a model for Down syndrome
Article first published online: 13 MAR 2009
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 42, Issue 2, pages 171–181, April 2009
How to Cite
Contestabile, A., Fila, T., Cappellini, A., Bartesaghi, R. and Ciani, E. (2009), Widespread impairment of cell proliferation in the neonate Ts65Dn mouse, a model for Down syndrome. Cell Proliferation, 42: 171–181. doi: 10.1111/j.1365-2184.2009.00587.x
- Issue published online: 13 MAR 2009
- Article first published online: 13 MAR 2009
- Received 4 February 2008; revision accepted 26 May 2008
Objectives: Among the many pathological aspects of Down syndrome, brain hypoplasia and mental retardation have been recently ascribed to defective proliferation of neural precursors during central nervous system development. By analogy, other features of Down syndrome, such as heart defects, gastrointestinal abnormalities, craniofacial dystrophy and reduced growth rate could be related, at least in theory, to similar proliferation impairment in peripheral tissues.
Materials and methods: In order to test this hypothesis, we evaluated cell proliferation in peripheral tissues of the Ts65Dn mouse, one of the animal models most commonly used to investigate Down syndrome.
Results: In fibroblast cultures from neonatal Ts65Dn mice, we found that cell proliferation was notably impaired. While length of the cell cycle was similar in fibroblasts from Ts65Dn and control mice, the number of actively proliferating cells was significantly smaller in Ts65Dn mice. Moreover, fibroblasts from Ts65Dn animals exhibited limited population-doubling capacity, decreased proliferative lifespan and premature senescence. Analysis of cell proliferation in the skin of neonates, in vivo, showed that in Ts65Dn mice, cell proliferation was significantly reduced compared to control mice.
Conclusions: Our results suggest that defective proliferation may be a generalized feature of trisomic mice. In view of the genetic and phenotypic similarities between Ts65Dn mice and individuals with Down syndrome, proliferation impairment in various organs may also occur in subjects with Down syndrome. Thus, perturbation of a basic developmental function, cell proliferation, may be a critical determinant that contributes to the many aspects of pathology of this condition.