An Adult Mouse Model of Dilated Cardiomyopathy Caused by Inducible Cardiac-Specific Bis Deletion.
Hye Hyeon YunSoon Young JungBong Woo ParkJi Seung KoKyunghyun YooJiyoung YeoHong Lim KimHun-Jun ParkHo Joong YounJeong Hwa LeePublished in: International journal of molecular sciences (2021)
BCL-2 interacting cell death suppressor (BIS) is a multifunctional protein that has been implicated in cancer and myopathy. Various mutations of the BIS gene have been identified as causative of cardiac dysfunction in some dilated cardiomyopathy (DCM) patients. This was recently verified in cardiac-specific knock-out (KO) mice. In this study, we developed tamoxifen-inducible cardiomyocyte-specific BIS-KO (Bis-iCKO) mice to assess the role of BIS in the adult heart using the Cre-loxP strategy. The disruption of the Bis gene led to impaired ventricular function and subsequent heart failure due to DCM, characterized by reduced left ventricular contractility and dilatation that were observed using serial echocardiography and histology. The development of DCM was confirmed by alterations in Z-disk integrity and increased expression of several mRNAs associated with heart failure and remodeling. Furthermore, aggregation of desmin was correlated with loss of small heat shock protein in the Bis-iCKO mice, indicating that BIS plays an essential role in the quality control of cardiac proteins, as has been suggested in constitutive cardiac-specific KO mice. Our cardiac-specific BIS-KO mice may be a useful model for developing therapeutic interventions for DCM, especially late-onset DCM, based on the distinct phenotypes and rapid progressions.
Keyphrases
- left ventricular
- heart failure
- ionic liquid
- late onset
- cell death
- cardiac resynchronization therapy
- hypertrophic cardiomyopathy
- high fat diet induced
- heat shock protein
- mouse model
- acute myocardial infarction
- quality control
- aortic stenosis
- atrial fibrillation
- early onset
- left atrial
- gene expression
- pulmonary hypertension
- squamous cell carcinoma
- wild type
- adipose tissue
- angiotensin ii
- coronary artery disease
- signaling pathway
- transcatheter aortic valve replacement
- protein kinase
- acute coronary syndrome
- duchenne muscular dystrophy
- type diabetes
- end stage renal disease
- cancer therapy
- prognostic factors