Trisomy 21 in patients with DS results in increased activity of an important antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the 21st chromosome along with other proteins such as transcription factor Ets-2, stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible for the formation of amyloid plaques in Alzheimer disease.
Recent work with the Ts65Dn model of DS, which has orthologues of about 50% of the genes on chromosome 21 (Hsa21), has indicated that three copies of the ETS2 (ref.
These results suggest that ETS2 expression is linked to the biology of AMkL in both DS and non-DS children, and that ETS2 acts by regulating expression of hematopoietic lineage and transcription factor genes involved in erythropoiesis and megakaryopoiesis, and in chemotherapy sensitivities.
These results highlight DS as a model to understand the role of APOE4 allele in unsuccessful ageing considering that a number of proinflammatory supernumerary genes (Cu/Zn superoxide dismutase, Ets-2 transcription factors, Down syndrome critical region 1, stress-inducible factor, interferon-alpha receptor and the amyloid precursor protein) are located on chromosome 21 and are implied in the pathologic processes of DS.
We selected a mouse model of trisomy 21 (TRS21): transgenic mice carrying extra copies of a HSA21 region corresponding to the D21S17-ETS2 region (previously referred to as "Down syndrome critical region 1").
Strong ets-2 immunoreactivity was observed in DS/AD and sporadic AD brains associated with degenerative markers such as bax, intracellular Abeta, and hyperphosphorylated tau.
Indeed we report for the first time that the ETS2 overexpression transgenic mouse develops a smaller thymus and lymphocyte abnormalities similar to that observed in DS.
We conclude that ETS2 is a transcriptional regulator of beta-APP and that overexpression of ETS2 in DS may play a role in the pathogenesis of the brain abnormalities in DS and possibly AD.
Here we show that Ets-2, a transcription factor located on human chromosome 21 and already overexpressed in multiple tissues in Down syndrome (DS, trisomy 21), is induced by low concentrations of hydrogen peroxide.
These results indicate that Ets2 has an important role in skeletal development and that Ets2 overexpression in transgenics is responsible for the genesis of the same type of skeletal abnormalities that are seen in Down's syndrome.
Decreased ETS2 transcripts found in temporal and frontal lobe of patients with Down Syndrome, however, may be involved in the pathogenesis of Down Syndrome including specific neurodegenerative processes and deteriorated plasticity of the brain taking place in Down Syndrome brain, as the concerted action of transcription factors may be seriously impaired.
This is the first report to clearly show that no overexpression of ets-2 can be found in heart of patients with DS, thus providing evidence against the current gene dosage effect-hypothesis.
In an effort to contribute to the construction of a transcriptional map of the DS CHD region we have performed direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and cDNAs synthesised from fetal heart structures.
The authors hypothesize that an excess of luteinizing hormone and follicle-stimulating hormone gonadotropins and overexpression of the Ets-2 gene through gene dosage effect could predispose patients with DS to the development of TGCT.
Our results indicate that Ets2 has a role in skeletal development and implicate the overexpression of Ets2 in the genesis of some skeletal abnormalities that occur in Down's syndrome.
In addition, the role of c-ets-2 in cell proliferation and its location in the minimal Down syndrome region on chromosome 21 implicates its involvement in the phenotypic changes associated with Down syndrome.
Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region.