APOL1 kidney risk variants in glomerular diseases modeled in transgenic mice.
Teruhiko YoshidaKhun Zaw LattBriana A SantoShashi ShrivastavYongmei ZhaoParide FenaroliJoon-Yong ChungStephen M HewittVincent M TutinoPinaki SarderAvi Z RosenbergCheryl A WinklerJeffrey B KoppPublished in: bioRxiv : the preprint server for biology (2023)
Coding variants in APOL1, encoding apolipoprotein L1, contribute to kidney disease in individuals with African ancestry. The mechanisms for glomerular injury remain incompletely understood. We studied two transgenic mouse models, HIV-associated nephropathy and interferon-ψ administration. Using glomerular and single-nuclear RNA sequencing, we identified genes differentially expressed among mice with kidney risk alleles (G1) and the common variant (G0). Both models exhibited up-regulation of genes that indicated podocyte damage with risk alleles compared to the common variant. One gene down-regulated in both models was Zbtb16, encoding a transcription factor, that may contribute to glucocorticoid-resistance. Overall, the findings suggest both shared and distinct alterations in the two disease models.
Keyphrases
- transcription factor
- copy number
- diabetic nephropathy
- genome wide
- genome wide identification
- hiv infected
- antiretroviral therapy
- single cell
- mouse model
- metabolic syndrome
- type diabetes
- human immunodeficiency virus
- gene expression
- adipose tissue
- dna methylation
- hiv testing
- dna binding
- immune response
- men who have sex with men
- insulin resistance