Alport syndrome is a hereditary disorder of the basement membrane, resulting in a glomerulonephropathy causing renal failure. Progressive deafness and ocular anomalies may also occur. Patients with Alport syndrome are reported to show mutations in collagen IV genes. Mice homozygous for the Col4A3-/- targeted mutation are a model of autosomal-recessive Alport syndrome. Animals are bred on a 129/SvJ background and develop glomerulonephritis (Jackson Laboratory strain: #002908).
The most important characteristics of Col4A3-/- mice are:
- Severely reduced survival time
- Increased smooth muscle actin levels in the renal cortex
- Increased albumin levels in the urine
Col4A3-/- mice present an increased immunoreactive area of smooth muscle actin that can be reduced to almost baseline levels by Ramipril treatment (Fig. 1).
Figure 1: Smooth muscle actin (SMA) labeling in the renal cortex of Col4A3-/- mice. SMA immunoreactive area in percent. Mean + SEM; n = 5 per group; One-way ANOVA with Bonferroni’s post hoc test; **p<0.01; ***p<0.001.
Evaluation of the urine of Col4A3-/- mice shows highly increased albumin levels that can be reduced by Ramipril treatment (Fig. 2)
Figure 2: Quantification of albumin in urine samples. Logarithmic presentation of albumin levels measured in urine samples collected at 4 time points (treatment day 0, 10, 20, and 28). Two-way ANOVA with Bonferroni’s post hoc test. Mean ± SEM; n = 6 per group; *Col4a3-/- Vehicle vs. WT-Vehicle; #Col4a3-/- Ramipril vs. Col4a3-/- Vehicle; *p<0.05; ***p<0.001.
QPS Neuropharmacology offers a custom-tailored study design for Col4a3-/- mice, and we are flexible to accommodate your special interests. We are also happy to advise you and propose study designs. Col4a3-/- mice show a relevant Alport syndrome phenotype at 6 weeks of age. This grants a remarkable fast processing time of your Alport syndrome study. Furthermore, wild type littermates are available as control animals needed for proper study design.
We are happy to evaluate the efficacy of your compound in the Col4a3-/- mouse model! The most common readouts are:
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QPS Neuropharmacology is ready to provide samples (e. g. kidney) from Col4a3-/- mice for analyses in your laboratory.