Document Type
Article
Publication Date
5-1-2026
Original Citation
Willey C,
Bufi R,
Takemon Y,
Brackett A,
Warren A,
Spellacy S,
Gatti D,
Sheehan S,
Korstanje R.
NBL1 associates with renal phenotypes in mice, but partial Nbl1 reduction does not ameliorate kidney disease. Am J Physiol Renal Physiol. 2026;330(5):F582–f91.
Keywords
JMG, SS1, Animals, Phenotype, Mice, Knockout, Cisplatin, Kidney, Nephritis, Hereditary, Disease Models, Animal, Glomerular Filtration Rate, Male, Mice, Genetic Predisposition to Disease, Albuminuria
JAX Source
Am J Physiol Renal Physiol. 2026;330(5):F582–f91.
ISSN
1522-1466
PMID
41910154
DOI
https://doi.org/10.1152/ajprenal.00465.2025
Grant
This work was supported by NIH Grants T32GM132006 (to C.N.W.) and R01DK131019 (to R.K.)
Abstract
Increased concentrations of neuroblastoma suppressor of tumorigenicity 1 (NBL1) in the blood have been associated with disease progression in diabetic kidney disease (DKD) and IgA nephropathy. However, it is unclear whether NBL1 is a causal factor for kidney disease and what is driving these increased concentrations in the blood. To test this, we evaluated Nbl1 heterozygous knockout (Nbl1+/−) mice in two models of kidney injury, X-linked Alport syndrome (XLAS) and chronic low-dose cisplatin treatment, and compared them with wild-type (WT) controls. In parallel, we assessed serum NBL1, kidney function, and damage, and performed a genetic analysis for the drivers of NBL1 concentrations in two independent cohorts of genetically diverse Diversity Outbred mice with XLAS (DO-XLAS), analyzing each cohort separately. Serum NBL1 was consistently associated with reduced glomerular filtration rate (GFR) across both DO-XLAS cohorts, whereas correlations with albumin-to-creatinine ratio (ACR) were variable between cohorts, and not consistently replicated. In both XLAS and cisplatin models, partial reduction of NBL1 (∼50%) in Nbl1+/− mice did not alter GFR, ACR, or histological injury relative to WT controls. Genetic analysis of NBL1 concentrations in our DO-XLAS cohorts identified associations with loci on Chromosomes 4 and 17. Together, these findings indicate that elevated serum NBL1 reflects kidney injury and, under partial reduction, does not alter disease severity, consistent with NBL1 functioning as a biomarker rather than a causal driver of kidney disease.
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