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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Phenotypic reversal of the btnl defects in yeast by chloroquine: A yeast model for Batten disease
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Phenotypic reversal of the btnl defects in yeast by chloroquine: A yeast model for Batten disease

机译：氯喹逆转酵母中btnl缺陷的表型：巴顿病的酵母模型

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摘要

BTN1 of Saccharomyces cerevisiae encodes an ortholog of CLN3, the human Batten disease gene. We have reported previously that deletion of BTN1, btnl-#delta#, resulted in a pH-dependent resistance to D-(-)-threo-2-amino-1-[p- nitrophenyl]-l,3-propanediol (ANP). This phenotype was caused by btnl-#delta# strains having an elevated ability to acidify growth medium through an elevated activity of the plasma membrane H~+-ATPase, resulting from a decreased vacuolar pH during early growth. We have determined that growing btml-#delta# strains in the presence of chloroquine reverses the resistancc to ANP, decreases the rate of medium acidification, decreases the activity of plasma membrane H~+-ATPase, and elevates vacuolar pH. However, an additional effect of this phenotypic reversal is that activity of plasma membrane H~+-ATPase is decreased further and vacuolar pH is increased further as btnl-A strains continue to grow. This phenotypic reversal of btnl-A can be considered for developing a therapy for Batten disease.
机译：酿酒酵母的BTN1编码人类巴顿病基因CLN3的直系同源基因。我们以前曾报道过，删除BTN1，btnl-＃delta＃，导致对D-（-）-苏式-2-氨基-2-氨基-1- [对硝基苯基] -1,3-丙二醇（ANP）的pH依赖性耐药）。此表型是由btnl-＃delta＃菌株引起的，该菌株具有通过质膜H + -ATPase活性升高而酸化生长培养基的能力，这是由于早期生长期间液泡pH降低所致。我们已经确定，在氯喹存在下生长的btml-＃delta＃菌株可以逆转对ANP的抵抗，降低培养基酸化的速率，降低质膜H〜+ -ATPase的活性，并提高液泡的pH。然而，这种表型逆转的另一个效果是，随着btnl-A菌株的不断生长，质膜H〜+ -ATPase的活性进一步降低，液泡pH进一步提高。可以考虑将btnl-A的这种表型逆转用于开发Batten疾病的疗法。

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