Department of Animal and Food Sciences, University of Delaware, Newark, DE, 19716, USA.
Present Address: Department of Animal Science, The Pennsylvania State University, University Park, PA, 16802, USA.
BMC Genomics. 2018 Mar 5;19(1):177. doi: 10.1186/s12864-018-4568-2.
A strain of Leghorn chickens (rd/rd), unable to produce a functional riboflavin-binding protein, lays riboflavin-deficient eggs, in which all embryos suddenly die at mid-incubation (days 13-15). This malady, caused by riboflavin deficiency, leads to excessive lipid accumulation in liver, impaired β-oxidation of lipid, and severe hypoglycemia prior to death. We have used high-density chicken microarrays for time-course transcriptional scans of liver in chicken embryos between days 9-15 during this riboflavin-deficiency-induced metabolic catastrophe. For comparison, half of rd/rd embryos (n = 16) were rescued from this calamity by injection of riboflavin just prior to incubation of fertile eggs from rd/rd hens.
No significant differences were found between hepatic transcriptomes of riboflavin-deficient and riboflavin-rescued embryos at the first two ages (days 9 and 11). Overall, we found a 3.2-fold increase in the number of differentially expressed hepatic genes between day 13 (231 genes) and day 15 (734 genes). Higher expression of genes encoding the chicken flavoproteome was more evident in rescued- (15 genes) than in deficient-embryos (4 genes) at day 15. Diminished activity of flavin-dependent enzymes in riboflavin-deficient embryos blocks catabolism of yolk lipids, which normally serves as the predominant source of energy required for embryonic development.
Riboflavin deficiency in mid-stage embryos leads to reduced expression of numerous genes controlling critical functions, including β-oxidation of lipids, blood coagulation and feathering. Surprisingly, reduced expression of feather keratin 1 was found in liver of riboflavin-deficient embryos at e15, which could be related to their delayed feathering and sparse clubbed down. A large number of genes are expressed at higher levels in liver of riboflavin-deficient embryos; these up-regulated genes control lipid storage/transport, gluconeogenesis, ketogenesis, protein catabolism/ubiquitination and cell death.
由于无法产生功能性核黄素结合蛋白，来航鸡（rd/rd）品系产下的蛋缺乏核黄素，所有胚胎在孵化中期（第 13-15 天）突然死亡。这种由核黄素缺乏引起的疾病导致肝脏中脂质过度积累、脂质β-氧化受损，以及在死亡前发生严重低血糖。在这种核黄素缺乏诱导的代谢灾难期间，我们使用高密度鸡微阵列对第 9-15 天的鸡胚肝脏进行了时间过程转录扫描。为了比较，在孵化来航鸡 rd/rd 母鸡的受精卵之前，向一半 rd/rd 胚胎（n=16）注射核黄素，使它们从这种灾难中获救。
在最初的两个年龄（第 9 天和第 11 天），缺乏核黄素和核黄素挽救的胚胎的肝转录组之间没有发现显著差异。总体而言，我们发现第 13 天（231 个基因）和第 15 天（734 个基因）之间差异表达的肝基因数量增加了 3.2 倍。在第 15 天，挽救组（15 个基因）比缺乏组（4 个基因）中编码鸡黄素蛋白组的基因表达更高。核黄素缺乏的胚胎中黄素依赖性酶的活性降低会阻止卵黄脂质的分解代谢，而卵黄脂质通常是胚胎发育所需的主要能量来源。
中期胚胎中的核黄素缺乏会导致控制关键功能的许多基因表达减少，包括脂质β-氧化、血液凝固和羽毛形成。令人惊讶的是，在核黄素缺乏的胚胎肝脏中发现了角蛋白 1 的表达减少，这可能与它们延迟的羽毛生长和稀疏的羽毛有关。大量基因在核黄素缺乏的胚胎肝脏中表达更高；这些上调的基因控制脂质储存/转运、糖异生、酮生成、蛋白质分解/泛素化和细胞死亡。
