Analysis for putative relationship between causative genes for hereditary disorder and quantitative traits loci in cattle

对R664X突变所致的带3缺陷表型与饱和/不饱和脂肪酸含量之间的关系进行了评估，饱和/不饱和脂肪酸是影响牛肉风味的主要因素。尽管带3缺陷携带者的油酸等不饱和脂肪酸的水平似乎高于正常动物，但表型/基因型与牛肉品质之间没有直接联系。此外，我们没有直接证据证明Claudin-16缺乏症的纯合子/杂合子状态具有显著优势。然而，本研究证实了调节位于19号染色体上的脂肪酸含量的遗传因素，并提示其与脂肪死亡有关。带3缺失的分子病理生物学研究结果表明，突变带3(BebRX)对正常带3及其膜骨架的配对Ankyrin的表达起着显性-负向作用，并且带3与ankyrin的相互作用发生在带3合成后不久的红细胞膜上。红系和肾小管上皮细胞带3的全部或部分缺失可能导致酸中毒，导致细胞代谢下调。在MDCK细胞中表达的Claudin-16显示了包括钙离子在内的离子和溶质的胞外转运的全面减少，而它似乎形成了细胞间的钙通道，这表明除了Claudin-1/4之外，Claudin-16与其他Claudin蛋白的异嗜性结合可能是形成钙分子孔所必需的。

A putative relationship between phenotypes for band 3 deficiency with the R664X mutation and contents of saturated/unsaturated fatty acids, which predominantly affect flavor and taste of beef, was evaluated. There was no direct linkage between phenotype/genotype and beef quality although carriers for band 3 deficiency appeared to have unsaturated fatty acids such as oleic acid at levels higher than normal animals. Moreover, we could not obtain direct evidence for remarkable advantage of homozygous/heterozygous states for claudin-16 deficiency. Present study, however, demonstrated a genetic factor that would regulate fatty acid contents located in chromosome 19, and suggested its linkage with fatnecrosis.The findings on molecular pathobiology of band 3 deficiency indicated that the mutant band 3 (bebRX) plays a dominant-negative role on the expression of normal band 3 and a partner in the membrane skeleton, ankyrin, and the interaction of band 3 with ankyrin occurs on the ER membrane soon after band 3 synthesis is started during erythroid development. Total or partial deficiency of band 3 in erythroid and renal tubular cells appeared to cause acidosis, leading to downregulation of cell metabolism. Claudin-16 expressed in MDCK cells displayed overall reduction in paracellular transport of ions and solutes including calcium ion, while it appeared to form intercellular pathway for calcium, suggesting that heterophilic combinations of claudin-16 and other claudin proteins other than claudin-1/4 would be essential to formation of molecular pores for calcium.