Genetic background influences the impact of KLOTHO deficiency.
Genetic background influences the impact of KLOTHO deficiency.
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遗传背景影响 KLOTHO 缺陷的影响。
DOI：
10.1152/physiolgenomics.00094.2020
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发表时间：
2020
影响因子：
4.6
通讯作者：
Rogers,MelissaB
中科院分区：
文献类型：
--
作者：
Salloum,JawadS;Garsetti,DianeE;Rogers,MelissaB
遗传背景是一个关键但有时被忽视的因素，它深刻地影响着人类和疾病模型中的疾病易感性和表现。KLOTHO蛋白是一种重要的肾脏矿物质稳态调节因子，也是FGF23的辅助因子，在此我们发现，KLOTHO蛋白的缺乏会导致129S1/SvlmJ(129)和C57BL/6J(B6)小鼠不同的表型。与B6小鼠相比，129菌株受到的影响更严重，寿命缩短，体重减轻，肾脏钙化量增加。这些菌株的正反交F1对Klothopha型也有亲子效应，其中B6母亲和129父亲的F1 KLOTHO缺陷后代的肾脏钙化比129母亲和B6父亲的后代更多。对导致特定近交系小鼠不同表型的遗传结构进行比较和对比，可能会揭示影响慢性肾脏疾病的先前未被认识的重要代谢相互作用。
Genetic background is a key but sometimes overlooked factor that profoundly impacts disease susceptibility and presentation in both humans and disease models. Here we show that deficiency of KLOTHO protein, an important renal regulator of mineral homeostasis and a cofactor for FGF23, causes different phenotypes in 129S1/SvlmJ (129) and C57BL/6J (B6) mouse strains. The 129 strain is more severely affected, with decreased longevity, decreased body weight, and increased amounts of kidney calcification compared with B6 mice. Reciprocal F1 crosses of the strains also indicate a parentage effect on theKlothophenotype with F1 KLOTHO-deficient progeny of B6 mothers and 129 fathers having more kidney calcification than progeny of 129 mothers and B6 fathers. Comparing and contrasting the genetic architecture leading to different phenotypes associated with specific inbred mouse strains may reveal previously unrecognized and important metabolic interactions affecting chronic kidney disease.