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Can zebrafish be a valid model to study P aget's disease of bone?
Author(s) -
Silva I. A. L.,
Conceição N.,
Michou L.,
Cancela M. L.
Publication year - 2014
Publication title -
journal of applied ichthyology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.392
H-Index - 62
eISSN - 1439-0426
pISSN - 0175-8659
DOI - 10.1111/jai.12523
Subject(s) - zebrafish , biology , protein data bank (rcsb pdb) , paget's disease of bone , danio , sequestosome 1 , synteny , genetics , gene , in silico , computational biology , mutation , bioinformatics , disease , genome , medicine , biochemistry , apoptosis , autophagy
Summary Paget's disease of bone ( PDB ) is the second most frequent metabolic bone disease after osteoporosis. Genetic factors play an important role in PDB , but to date the only PDB causal gene identified is the Sequestosome 1 ( SQSTM 1 ) gene. Because the zebrafish has been validated as a model for human genetic diseases, the objective was to investigate if the gene structure and chromosomal environment of the SQSTM 1 were similar between zebrafish and humans, thus providing a basis for developing a mutant fish capable of modeling PDB . Through a comparative in silico analysis, we confirmed that zebrafish sqstm1 shares not only the same gene structure as its fish and mammalian orthologs, but they also present, within their promoter regions, similar putative binding sites for common transcriptional factors known to affect bone metabolism. The synteny of SQSTM 1 was also determined and results indicate that the cluster of surrounding genes was conserved throughout evolution. The protein comparison revealed a high degree of conservation, particularly in the functional domains of the protein. The most common mutation in PDB patients is p.Pro392Leu and the residue Pro392 was found to be 100% conserved in all species analyzed, including zebrafish, confirming its known functional relevance. In conclusion, this study demonstrated that SQSTM 1 is well conserved throughout evolution and therefore fish models such as the zebrafish could be an interesting tool to further investigate the biological role of SQSTM 1 in PDB and in bone development.