A previous study suggested that human Coffin-Siris syndrome is related to the mutation of SOX11. Since the homozygous SOX11 mutant mice died soon after birth, no suitable model was available for the study of the pathogenic mechanism of Coffin-Siris syndrome. To solve this problem, we generated two viable homozygous zebrafish mutants, sox11a m/m and sox11b m/m. We found that the sox11a m/m mutant possessed Coffin-Siris syndrome features. The sox11a m/m mutants exhibited growth deficiency from 3.3 hpf embryos to adulthood. Furthermore, the sox11a m/m mutant also displayed microcephaly, narrow pupillary distance, achondroplasia, and bone deformity in adults. Growth deficiency could be rescued by the injection of sox11a mRNA at the one-cell stage. In addition, the expression levels of genes related to cartilage and bone were downregulated in the sox11a m/m mutant, indicating that sox11a mainly affected the growth and development of zebrafish by regulating the expression of genes related to skeletal development. Our results indicate that sox11a m/m mutant zebrafish offered a potential model system to help with the search for pathogenic mechanisms of human Coffin-Siris syndrome.

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This experiment investigated the effects of dietary starch on growth performance, feed utilization, glucose and lipid metabolism of non-transgenic and growth hormone (GH) transgenic juvenile common carp (Cyprinus carpio L.). Transgenic common carp (TG fish) and non-transgenic (NT fish) were fed diets with five starch levels (0, 10%, 20%, 30%, 40%). After 41 days, TG fish showed higher growth and feed utilization at low-starch diets, while similar growth, lower feeding rate (FR) and slightly higher feed efficiency (FE) was observed at high-starch diets. Lower plasma glucose level and hepatic glycogen content were observed in TG fish, which could be related to the higher glycolysis (high gene expression of hexokinase (hk), p < 0.01) and gluconeogenesis (high gene expression of fructose-1,6-bisphosphatase (fbpase), p < 0.01; glucose-6-phosphatase (g6pase), p < 0.01) of TG fish. Compared to NT fish, weakened fat synthesis (lower gene expression of fatty-acid synthase (fas), p <0.01; acetyl-CoA carboxylase 1 (acc1), p < 0.01; acyl-CoA desaturase 1 (scd1), p = 0.011) and enhanced fatty acid oxidation (high gene expression of hormonesensitive lipase (hsl), p =0.01; carnitine palmitoyl transferase 1a (cpt-1a), p < 0.01), led to the decrease of body lipid content in TG fish. On the other hand, with increased dietary starch, increased body lipid and hepatic glycogen contents were observed in both TG and NT fish, suggesting that high dietary starch levels promoted glycolysis, fat synthesis and inhibited gluconeogenesis, fatty acid β-oxidation. Overall, TG fish showed higher growth performance at low starch diets, and higher ability of glycolysis, fatty acid oxidation and lower lipid synthesis than the NT fish.

Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid β-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 ± 0.32 g) and WT (initial weight 3.30 ± 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 ± 0.33 g) and WT (initial weight 3.27 ± 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid β-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.

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Growth hormone (GH) is important for regulating insulin secretion and carbohydrate metabolism, and its role in mammalian models of diabetes is relatively worked out. Although some fish species were used as models for diabetes research, the effects of GH on insulin and glucose catabolism and anabolism in these models remain to be clarified. In this study, we investigated the effect of GH on insulin and glucose catabolism and anabolism in an omnivorous fish using GH transgenic (T) common carp that consistently overexpressed GH and wild-type (WT) common carp. We compared the intestinal morphology, and digestive and absorptive capacity of fish fed commercial feed. We also analyzed the growth performance, insulin level, glucose catabolism and anabolism, lipid deposition, and lipid catabolism and anabolism in T carp and WT carp fed diets containing either 30% or 40% starch. In the intestine of T carp, α-amylase activity was enhanced, the number of goblet cells and intestinal villi surface area was increased, and the expression level of glucose transport protein-related genes (glut2 and sglt1) was upregulated when compared to these indicators in WT carp. When fed either a normal or high-starch diet, the growth performance of T carp was better than that of WT carp. Compared with WT carp, serum insulin was increased and glucose was decreased, hepatic expression level of igf-1 and glycolysis-related genes was increased, and the activity level of a hepatic enzyme related to glycolysis was enhanced in T carp. When fed with a high-starch diet, the serum alanine aminotransferase activity, hepatic lipid content, and malondialdehyde content were significantly lower in T carp than in WT carp. These results indicated that overexpression of GH (1) enhanced carbohydrate digestion and absorption in the carp intestine, (2) did not induce insulin resistance and improved glucose catabolism and utilization in carp, and (3) relieved liver lipid deposition. Our data might provide new insights into potential ways to improve glucose utilization in fish and diabetes treatments.