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Publication : Genetic background influences the impact of KLOTHO deficiency.

First Author  Salloum JS Year  2020
Journal  Physiol Genomics Volume  52
Issue  10 Pages  512-516
PubMed ID  32956023 Mgi Jnum  J:324433
Mgi Id  MGI:6884529 Doi  10.1152/physiolgenomics.00094.2020
Citation  Salloum JS, et al. (2020) Genetic background influences the impact of KLOTHO deficiency. Physiol Genomics 52(10):512-516
abstractText  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 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.
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