The relationship between nephron number, kidney size and body weight in two inbred mouse strains

Abstract

While some reports in humans have shown that nephron number is positively correlated with height, body weight or kidney weight, other studies have not reproduced these findings. To understand the impact of genetic and environmental variation on these relationships, we examined whether nephron number correlates with body weight, kidney planar surface area, or kidney weight in two inbred mouse strains with contrasting kidney sizes but no overt renal pathology: C3H/HeJ and C57BL/6J. C3H/HeJ mice had smaller kidneys at birth and larger kidneys by adulthood, however there was no significant difference in nephron number between the two strains. We did observe a correlation between kidney size and body weight at birth and at adulthood for both strains. However, there was no relationship between nephron number and body weight or between nephron number and kidney size. From other studies, it appears that a greater than two-fold variation is required in each of these parameters in order to demonstrate these relationships, suggesting they are highly dependent on scale. Our results are therefore not surprising since there was a less than two-fold variation in each of the parameters examined. In summary, the relationship between nephron number and body or kidney size is most likely to be demonstrated when there is greater phenotypic variation either from genetic and/or environmental factors.

Keywords: B6; C3H; birth weight; hypertrophy; inbred; kidney size; mouse; nephron number.

Figure 1

Kidney size in C3H/HeJ and C57BL/6J mice at birth and at adulthood. (A) Two inbred mouse strains were identified as having contrasting kidney phenotypes at birth. C3H mice have significantly smaller kidneys when compared to B6 mice. C3H: 3.61 ± 0.06 mm²/g compared to B6: 4.18 ± 0.08 mm²/g (measured as planar surface area corrected for body weight ± SE, *p = 2 × 10⁻⁷). (B) By adulthood, C3H kidneys are larger than B6 kidneys. C3H: 2.67 ± 0.05 mm²/g compared to B6: 2.27 ± 0.02 mm²/g (measured as planar surface area corrected for body weight ± SE, *p = 1.8 × 10⁻⁷).

Figure 2

Nephron number, kidney size and birth weight in newborn mice. (A) A positive correlation between kidney weight and kidney planar surface area is seen in the newborn period when combining data from C3H and B6 mice (R² = 0.7412, p = 4 × 10⁻⁹, n = 28). (B) A positive correlation is observed between kidney weight and birth weight in newborn C3H and B6 mice (R² = 0.406, p = 1.2 × 10⁻⁴, n = 28). (C) Nephron number does not correlate with birth weight in newborn C3H and B6 mice (R² = 0.0062, p = 0.7, n = 26). (D) Similarly, nephron number does not correlate with kidney weight in newborn C3H and B6 mice (R² = 0.0098, p = 0.63, n = 26).

Figure 3

Nephron number and glomerular tuft size in adult mice. (A) Estimated nephron number in all C3H and B6 adult kidneys, males and females, are shown as mean ± SE. C3H kidneys have the same nephron counts as B6 kidneys. C3H: 20220 ± 684 nephrons (n = 24) vs. B6: 21085 ± 779 nephrons (n = 24) (p = 0.4). (B) Estimated nephron number in males (M) and females (F) are shown as mean ± SE: C3H F (n = 12): 19591 ± 1116; B6 F (n = 12): 22830 ± 1117; C3H M (n = 12): 20848 ± 799; B6 M (n = 12): 19341 ± 859. Kidneys from B6 females have, on average, 13% more nephrons than any other group (*p = 0.05). (C) Glomerular surface area in B6 and C3H males (M) and females (F) are shown as mean ± SE: C3H F: 0.002353 ± 0.000061 mm²; B6 F: 0.002094 ± 0.000045 mm²; C3H M: 0.002408 ± 0.000062 mm²; B6 M: 0.00226 2 ± 0.000068 mm². B6 females have glomerular tufts that are, on average, 12% smaller than those seen in all other groups (*p = 0.003).

Figure 4

Nephron number, kidney size and body weight in adult mice. (A) Nephron number does not correlate with body weight in adult C3H and B6 mice (R² = 3 × 10⁻⁵, p = 0.97, n = 48). (B) Nephron number does not correlate with kidney weight in adult C3H and B6 mice (R2 = 0.0068, p = 0.58, n = 48).