Shriners Hospital for Children-Canada, Montreal, QC H4A 0A9, Canada.
Department of Pediatrics, McGill University, Montreal, QC H4A 3J1, Canada.
Int J Mol Sci. 2021 May 18;22(10):5290. doi: 10.3390/ijms22105290.
Osteogenesis imperfecta (OI) is a bone fragility disorder that is usually caused by mutations affecting collagen type I. We compared the calvaria bone tissue transcriptome of male 10-week-old heterozygous Jrt ( mutation) and homozygous mice ( mutation) to their respective littermate results. We found that Jrt and mice shared 185 differentially expressed genes (upregulated: 106 genes; downregulated: 79 genes). A total of seven genes were upregulated by a factor of two or more in both mouse models (, , , , , and ). One gene (, coding for a blood group antigen) was downregulated by a factor of two or more in both OI mouse models. Overrepresentation analyses revealed that genes involved in 'ossification' were significantly overrepresented among upregulated genes in both Jrt and mice, whereas hematopoietic genes were downregulated. Several genes involved in Wnt signaling and transforming growth factor beta signaling were upregulated in mice, but less so in Jrt mice. Thus, this study identified a set of genes that are dysregulated across various OI mouse models and are likely to play an important role in the pathophysiology of this disorder.
成骨不全症（OI）是一种骨骼脆弱疾病，通常由影响 I 型胶原的突变引起。我们比较了 10 周龄雄性杂合子 Jrt（突变）和纯合子 小鼠（突变）的颅骨骨组织转录组与其各自的同窝仔结果。我们发现 Jrt 和 小鼠共有 185 个差异表达基因（上调：106 个基因；下调：79 个基因）。在两个小鼠模型中，共有七个基因的表达上调了两倍或更多（、、、、、和）。一个基因（编码血型抗原）在两个 OI 小鼠模型中均下调了两倍或更多。过度表达分析显示，在 Jrt 和 小鼠中上调的基因中，与“骨化”相关的基因显著富集，而造血基因则下调。一些参与 Wnt 信号和转化生长因子 β 信号的基因在 小鼠中上调，但在 Jrt 小鼠中上调程度较低。因此，这项研究确定了一组在各种 OI 小鼠模型中失调的基因，这些基因可能在该疾病的病理生理学中发挥重要作用。
