Abstract
Low nephron endowment is associated with hypertension and chronic kidney disease. We compared recovered glomerular counts and kidney mass across four mouse strains at 8 weeks of age and examined age-associated phenotypes and developmental kidney transcriptomes in FVB/N and C57BL/6J mice. Sex-adjusted models allowing for strain-specific variances showed lower recovered counts and counts per gram of kidney in FVB/N than in the other strains. Proportional scaling with kidney mass was not supported. After adjustment for kidney weight, differences remained significant relative to BALB/c and DBA/2, whereas the difference from C57BL/6J remained unresolved. These measurements do not establish absolute nephron endowment. In independent groups of males of different ages, FVB/N mice showed greater glomerular enlargement and higher semiquantitative urinary albumin-to-creatinine ratios. Strain-matched developmental RNA-seq attenuated measurable reference-genome effects. Deconvolution using either the P1 or E14.5 single-cell reference detected no strain difference in the estimated progenitor proportion at E13.5, although absolute estimates were reference-dependent. No coordinated GDNF–RET downregulation or significant kidney-related enrichment was detected. Integration of regulatory annotations prioritised five genes as exploratory candidates. Lower interferon-related expression in FVB/N at P1 was consistent across samples and leave-one-out analyses. Developmental phenotyping and independent genetic validation are needed to establish the origins of these strain differences.