Premium
Upregulation of beta‐catenin expression in Down syndrome model Ts65Dn mouse brain and human Down syndrome brain
Author(s) -
Ramakrishrayan
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a649-d
Subject(s) - chromosome 21 , trisomy , biology , down syndrome , downregulation and upregulation , human brain , catenin , gene , blot , gene expression , chromosome , northern blot , microbiology and biotechnology , wnt signaling pathway , genetics , neuroscience
Trisomy of human chromosome 21 causes the pathological characteristics of Down syndrome (DS). Little is known about the mechanisms by which trisomy 21 affects the expression of genes on other chromosomes. We have used a mouse model of DS, the Ts65Dn mouse, and RT‐PCR and western blotting techniques, to identify genes on chromosomes nonsyntenic with human chromosome 21 which are affected by the presence of three copies of the Down syndrome critical region genes. We report the up‐regulation in the brains of these mice of both ß‐catenin mRNA and protein. The ß‐catenin gene is located on mouse chromosome 9, a chromosome nonsyntenic with human chromosome 21. Using immunocytochemistry on Ts65Dn and control mouse brain tissue, we observed a striking increase in ß‐catenin expression specifically in the endothelial cells lining the cerebral blood vessels of the Ts65Dn mice compared to the controls. A similar up‐regulation of ß‐catenin gene expression in adult human Down syndrome brain is evident from western blot results. Since ß‐catenin is involved in the cell‐cell adhesion it is possible that up regulation of this protein in DS may be related to alterations in cell adhesion leading to changes in tight junction protein interactions and permeability of affected capillaries.