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Genetic Background Influences the Impact of KLOTHO Deficiency.
Physiological Genomics  (IF3.107),  Pub Date : 2020-09-21, DOI: 10.1152/physiolgenomics.00094.2020
Jawad S Salloum,Diane E Garsetti,Melissa B Rogers

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 to B6 mice. Reciprocal F1 crosses of the strains also indicate a parentage effect on the Klotho phenotype 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.