疾病和发育的斑马鱼模型研究

基于斑马鱼在眼科疾病研究的优势以及精准医疗的需要，率先应用基因编辑的方法，建立了世界上品种最多的视网膜色素变性致病基因突变的斑马鱼模型。目前已成功在斑马鱼中分别敲除RP2，CERKL, EYS，PRPF31，PROM1，RPGR，NRL，NR2E3，PRP16，USH2A，CYP4V7等20多种重要的RP致病基因，得到这些基因突变的多种RP品系。这些模式动物的获得，为便利地观察分析基因突变导致视网膜变性的早期、中期和晚期的病理发展过程及其病理特征，分析这些不同基因突变导致视网膜细胞结构和功能变化与疾病发生之间的关系及其生化途径，为阐明不同基因突变最终导致视网膜感光细胞变性的分子机制打下了良好基础，为发展针对不同基因突变引起的RP，寻找相同的或不同的预防和治疗方法，率先开展这些遗传性眼科疾病的精准医疗研究创造了良好的条件。

斑马鱼是研究早期胚胎发育的最佳模式动物之一，课题组利用斑马鱼体外受精和发育的优势，研究早期胚胎发育过程中组织器官发育和分化的调控机制，包括血液系统、视网膜等组织器官发育和分化的调控信号通路和分子机制，探讨发育与疾病的相互关系。

代表性论文：

1、Han Y, Sun K, Yu S, Qin Y, Zhang Z, Luo J, Hu H, Dai L, Cui M, Jiang C, Liu F, Huang Y, Gao P, Chen X, Xin T, Ren X, Wu X, Song J, Wang Q, Tang Z, Chen J, Zhang H, Zhang X*, Liu M*, Luo D*. A Mettl16/m⁶A/mybl2b/Igf2bp1 axis ensures cell cycle progression of embryonic hematopoietic stem and progenitor cells. EMBO J. 2024 May;43(10):1990-2014.

2、Lv Y, Li J, Yu S, Zhang Y, Hu H, Sun K, Jia D, Han Y, Tu J, Huang Y, Liu X, Zhang X, Gao P, Chen X, Shaw Williams MT, Tang Z, Shu X, Liu M*, Ren X*. The splicing factor Prpf31 is required for hematopoietic stem and progenitor cell expansion during zebrafish embryogenesis. J Biol Chem. 2024 Feb 19:105772.

3、Jia D, Gao P, Lv Y, Huang Y, Reilly J, Sun K, Han Y, Hu H, Chen X, Zhang Z, Li P, Luo J, Shu X, Tang Z, Liu F, Liu M*, Ren X*. Tulp1 deficiency causes early-onset retinal degeneration through affecting ciliogenesis and activating ferroptosis in zebrafish. Cell Death Dis. 2022 Nov 17;13(11):962.

4、Tu J, Yu S, Li J, Ren M, Zhang Y, Luo J, Sun K, Lv Y, Han Y, Huang Y, Ren X, Jiang T, Tang Z, Williams MTS, Lu Q*, Liu M*. Dhx38 regulates the maintenance and differentiation of erythro-myeloid progenitors and hematopoietic stem cells by alternative splicing. Development. 2022 Aug 5:dev.200450.

5、Liu F, Qin Y, Huang Y, Gao P, Li J, Yu S, Jia D, Chen X, Lv Y, Tu J, Sun K, Han Y, Reilly J, Shu X, Lu Q, Tang Z, Xu C*, Luo D*, Liu M. Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration. PLoS Genet. 2022 Mar 4;18(3):e1009841

6、Gao P, Jia D, Li P, Huang Y, Hu H, Sun K, Lv Y, Chen X, Han Y, Zhang Z, Ren X, Wang Q, Liu F, Tang Z*, Liu M*. Accumulation of Lipid Droplets in a Novel Bietti Crystalline Dystrophy Zebrafish Model With Impaired PPARα Pathway. Invest Ophthalmol Vis Sci. 2022 May 2;63(5):32.

7、Li J, Liu F, Lv Y, Sun K, Zhao Y, Reilly J, Zhang Y, Tu J, Yu S, Liu X, Qin Y, Huang Y, Gao P, Jia D, Chen X, Han Y, Shu X, Luo D, Tang Z*, Liu M*. Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing. Nucleic Acids Res. 2021 Feb 26;49(4):2027-2043.

8、Yu S, Jiang T, Jia D, Han Y, Liu F, Huang Y, Qu Z, Zhao Y, Tu J, Lv Y, Li J, Hu X, Lu Z, Han S, Qin Y, Liu X, Xie S, Wang QK, Tang Z, Luo D*, Liu M*. BCAS2 is essential for hematopoietic stem and progenitor cell maintenance during zebrafish embryogenesis. Blood. 2019 Feb 21;133(8):805-815

9、Hu X, Lu Z, Yu S, Reilly J, Liu F, Jia D, Qin Y, Han S, Liu X, Qu Z, Lv Y, Li J, Huang Y, Jiang T, Jia H, Wang Q, Liu J, Shu X, Tang Z*, Liu M*. CERKL regulates autophagy via the NAD-dependent deacetylase SIRT1. Autophagy. 2019 Mar;15(3):453-465.

 10、Lu Z, Hu X, Reilly J, Jia D, Liu F, Yu S, Liu X, Xie S, Qu Z, Qin Y, Huang Y, Lv Y, Li J, Gao P, Wong F, Shu X, Tang Z*, Liu M*. Deletion of the transmembrane protein Prom1b in zebrafish disrupts outer-segment morphogenesis and causes photoreceptor degeneration. J Biol Chem. 2019 Sep 20;294(38):13953-13963