| Autor: |
Gerdes Gyuricza I; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil., Barbosa de Souza R; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil., Farinha-Arcieri LE; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil., Ribeiro Fernandes G; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil., Veiga Pereira L; National Laboratory for Embryonic Stem Cells (LaNCE), Department of Genetics and Evolutionary Biology, Biosciences Institute, University of São Paulo, São Paulo, SP, 05508-900, Brazil. lpereira@usp.br. |
| Abstrakt: |
Marfan syndrome (MFS) is a connective tissue disease caused by variants in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mg∆ loxPneo mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here, we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mg∆ loxPneo mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients. |
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