Comparison between C57BL/6N and C57BL/6J for their systolic blood pressure and heart rate responses to various salt challenges measured by NIBP.

<p>Measurements were made during the dark periods of a modified light/dark cycle. NS = normal salt diet (n = 20 and n = 20, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 20 and n = 20, for C57BL/6N and C57BL/6J respectively), HS = high Na⁺/normal K⁺ diet (n = 9 and n = 10, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na⁺/low K⁺ diet (n = 9 and n = 10, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey Kramer’s post-hoc test; #: p<0.05 HS/LK compared to HS.</p

Plasma ion, aldosterone and renin activity measurements in C57BL/6N and C57BL/6J male mice.

<p>Plasma ion, aldosterone and renin activity measurements in C57BL/6N and C57BL/6J male mice.</p

Comparison between C57BL/6N and C57BL/6J for their mean blood pressure and heart rate responses to various salt challenges.

<p>Mice were monitored with telemetry during the dark (A, B) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17 and n = 17, for C57BL/6N and C57BL/6J respectively), LS = low salt diet (n = 15 and n = 17, for C57BL/6N and C57BL/6J respectively), HS = high Na⁺/normal K⁺ diet (n = 8 and n = 8, for C57BL/6N and C57BL/6J respectively) and HS/LK = high Na⁺/low K⁺ diet (n = 6 and n = 9, for C57BL/6N and C57BL/6J respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.</p

Effects of high-salt/normal potassium and high-salt/low potassium on mean blood pressure and heart rate in C57BL/6N mice.

<p>Mice were monitored with telemetry in the dark (A, B, C) and light (C) periods of a modified light/dark cycle. NS = normal salt diet (n = 17), LS = low salt diet (n = 15), HS = high Na⁺/normal K⁺ diet (n = 8) and HS/LK = high Na⁺/low K⁺ diet (n = 6). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet; #: p<0.05 HS/LK compared to HS.</p

Effect of high salt diets on the circadian blood pressure variations in C57BL/6N and C57BL/6J mice under a reverse light/dark cycle.

<p>2.5 days continuous telemetric recordings of systolic blood pressure after 2 weeks of NS, HS or HS/LK diet challenge. A) n = 8 per group B) n = 6 per group C) n = 8 per group D) n = 9 per group. Two-way ANOVA followed by Sidak’s post-hoc test *: p<0.05 for interaction.</p

Sodium and potassium levels in urine and plasma in C57BL/6N.

<p>Sodium and potassium levels in urine and plasma in C57BL/6N.</p

Effects of various salt challenges on mean blood pressure and heart rate in C57BL/6N male mice.

<p>Mice were monitored with telemetry and placed in a standard (A, C) or modified light/dark cycle (B, D). NS = normal salt diet (n = 12 and n = 17, for the standard and modified light cycle respectively), LS = low salt diet (n = 11 and n = 15, for the standard and modified light cycle respectively), HS = high Na⁺/normal K⁺ diet (n = 5 and n = 6, for the standard and modified light cycle respectively). One-way ANOVA per light phase followed by Tukey’s post-hoc test; *: p<0.05 compared to NS diet.</p

Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems