Osteo-chondroprogenitor-specific deletion of the selenocysteine tRNA gene, Trsp, leads to chondronecrosis and abnormal skeletal development: a putative model for Kashin-Beck disease.
Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA([Ser]Sec), required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome.
Downey
Charlene M
CM
The McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
Horton
Chelsea R
CR
Carlson
Bradley A
BA
Parsons
Trish E
TE
Hatfield
Dolph L
DL
Hallgrímsson
Benedikt
B
Jirik
Frank R
FR
D000818:Animals; D001848:Bone Diseases, Developmental / Q000235:genetics* / Q000378:metabolism; D001842:Bone and Bones / Q000002:abnormalities* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012345:RNA, Transfer, Amino Acid-Specific / Q000235:genetics* / Q000378:metabolism; D012643:Selenium / Q000172:deficiency; D051140:Selenoproteins / Q000378:metabolism
D012345:RNA, Transfer, Amino Acid-Specific; D051140:Selenoproteins; C036928:tRNA, selenocysteine-; D012643:Selenium
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