hoxa1a -Null Zebrafish as a Model for Studying HOXA1 -Associated Heart Malformation in Bosley-Salih-Alorainy Syndrome

• Published in: Biology (Basel, Switzerland) Vol. 12; no. 7; p. 899
• Main Authors: Wang, Hongjie, He, Jingwei, Han, Xuemei, Wu, Xiuzhi, Ye, Xuebin, Lv, Wenchao, Zu, Yao
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-06-2023; MDPI
• Subjects: Bosley–Salih–Alorainy syndrome; Cardiovascular diseases; Cartilage; Cell adhesion & migration; Congenital defects; Coronary artery disease; CRISPR; Danio rerio; EKG; Embryos; Ethanol; Genes; Genomes; Heart; Heart diseases; heart malformation; HOX gene; HOXA1 protein; hoxa1a; Hybridization; Morphogenesis; Morphology; Mutation; Myocardium; Photography; Physiology; Ventricle; Vertebrates; Zebrafish; United States > US; CRISPR; zebrafish; hoxa1a; Bosley–Salih–Alorainy syndrome; heart malformation
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12070899

Mutations in
can lead to diseases such as Bosley-Salih-Alorainy syndrome, involving severe cardiovascular malformations. However, the role of
in cardiac morphogenesis remains unclear.
is a homologous gene to human
in zebrafish. We used CRISPR to make
-null zebrafish that exhibited multiple heart malformations. In situ hybridization and sections revealed the morphological changes in mutants: enlarged ventricle with thickened myocardium and increased trabeculae, intensified OFT and inadequate heart looping, with electrocardiography supporting these pathological changes. High-speed photography captured cardiac pumping and revealed a significant decrease in cardiac output. Furthermore, lacking
led to posterior body abnormality that affected movement ability, corresponding with the motor development delay in patients. Upregulation of
paralogues in
-null fish implied a compensatory mechanism between
genes. Accordingly, we successfully constructed a
-null model with a cardiac disease pattern which occurred in human
-associated heart malformation. The study of
in zebrafish can further promote the understanding of
genes and related diseases.