Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice / 神经科学通报·英文版

Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.

Establishment of zebrafish model for non-alcoholic steatohepatitis / 中华肝脏病杂志

Objective@#To establish overfed zebrafish model for non-alcoholic steatohepatitis.@*Methods@#The wild-type zebrafish was fed 3 times a day with normal diet. Body length, weight, and triglyceride levels were measured after 20 days of feeding. The changes in expression of genes associated with cholesterol metabolism, lipid metabolism, endoplasmic reticulum stress, and inflammation were detected by quantitative PCR. Liver tissue sections were stained with H&E. Statistical analyses between groups were compared using t-test.@*Results@#The body length (0.71±0.014) cm and body weight (44.83±1.833) mg of model group were higher than that of control group (0.50±0.009) cm and body weight (19.33±2.753) mg (total body length = 12.36, total body weight = 7.71, P < 0.01). Triglyceride content in the model group was (59.15 ± 0.5612) μmol / L, higher than the control group (16.71 ± 0.3562) μmol / L (t = 63.84, P < 0.001). Quantitative PCR results showed that the expression of genes related to cholesterol synthesis in the model group was higher than that in the control group (P < 0.01). The expression levels of lipid production and lipid oxidation related factors in the model group were higher than the control group. The difference between the two groups was statistically significant (P < 0.05). The expression of inflammation-related factors in the model group was higher than that in the control group (P < 0.001), and the expression of genes related to endoplasmic reticulum stress in the model group was higher than that to control group (P<0.001). Liver H&E staining showed that the model group had pathological changes such as large bulla and vesicles compared to the control group.@*Conclusion@#A continuous 3 times 20 days of normal diet can simulate the disease characteristics of human non-alcoholic steatohepatitis in a zebrafish.

Role of Wnt/β-catenin signaling in zebrafish lateral line hair cell regeneration / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the role of Wnt/β-catenin signaling in hair cell regeneration using zebrafish lateral line system. METHODS Zebrafish larval were incubated in cisplatin solution to induce lateral line hair cells loss and then regenerated for 48 hrs. Supporting cells were sorted, and QPCR was taken to detect the expression change of Wnt/β-catenin signaling factors. Whole mount in situ hybridization was used to show the expression pattern of dkks. Wnt/β-catenin signalinginhibitors(FH535 and XAV939) and enhancer(BIO) was added to the medium to observe the influences on hair cell regeneration. RESULTS RT-PCR and Q-PCR showed that the expressions of wnt2, wnt3a and ctnnb1 in sorting supporting cells were elevated(P＜0.05). Whole mount in situ hybridization showed that the expression of dkk1a and dkk2 in lateral lines sub-supporting cellsreduced. The addition of Wnt/β-catenin signaling inhibitors reduced the regenerated hair cells to 40％ of normal, and even to 10％ when the concentration of inhibitor was elevated.And the first 12 hrs Wnt/β-catenin signaling inhibition also led to the reduced regenerated hair cells(P＜0.001). However, regeneratedhair cells have no significant change compared between BIO-treated and nontreated group(P＞0.05). CONCLUSION Wnt/β-catenin signaling is necessary whilenot sufficient for zebrafish lateral line hair cell regeneration.

Cell death type of zebrafish lateral line hair cellsinduced by cisplatin / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore cell death type of lateral line hair cellsinduced by cisplatin in zebrafish. METHODS Zebrafish larva were incubated in 1mM cisplatin solution for 6 hrs to induce about 90%lateral line hair cells loss. Time lapse imaging was used to detect the morphology of cisplatin-incubated hair cells in wildtypezebrafish pre-labelled by live dyes Bodipy TR C5-ceramide and Sytogreen 24. TUNEL assay and In situ anti-active Caspase-3 antibody staining were performed to detect nuclei fragmentation and Caspase-3 activity respectively. RESULTS Compared to control group, hair cells condensationand nuclei fragmentation (P<0.05) were detected in cisplatin-incubated group, and active Caspase-3 activity was also observed after cisplatin addition. CONCLUSION Cisplatinmay induced zebrafish lateral line hair cells loss by Caspase-3-dependent apoptotic pathway.