TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

• DOI: 10.1371/journal.pone.0227393
• Publication Date: 2020-04-01T17:29:51Z
• Authors: Nariaki Miyao; Yukiko Hata; Hironori Izumi; Ryo Nagaoka; Yuko Oku; Ichiro Takasaki; Taisuke Ishikawa; Shinya Takarada; Mako Okabe; Hideyuki Nakaoka; Keijiro Ibuki; Sayaka Ozawa; Tomoyuki Yoshida; Hideyuki Hasegawa; Naomasa Makita; Naoki Nishida; Hisashi Mori; Fukiko Ichida; Keiichi Hirono
• Keywords: Dilated Cardiomyopathy; Pathogenesis

TBX5 is a transcription factor that has an important role in development of heart. variants the region encoding T-box domain have been shown to cause cardiac defects, such as atrial septal defect or ventricular defect, while also identified few cardiomyopathy patients and considered causative. We variant (c.791G>A, p.Arg264Lys), over-represented patients. This located outside domain, its pathogenicity not confirmed by functional analyses.To investigate whether R264K deleterious could contribute pathogenesis cardiomyopathy.We developed mice expressing Tbx5 R264K. Mice homozygous for this displayed compensated dilated cardiomyopathy; mild decreased fractional shortening, dilatation left ventricle, wall thinning increased heart weight without major structural disorders. There was no difference activation ANF promotor, transcriptional target Tbx5, compared wild-type. However, analysis RNA isolated from samples showed significant increases expression Acta1 ventricle with concomitant protein level ACTA1.Mice cardiomyopathy. Thus, may pathogenic some independently pathway.