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 albumin levels in the urine
- Increased blood urea nitrogen in the plasma
- Increased smooth muscle actin levels in the renal cortex
Col4A3-/- mice present an increased urine albumine-creatinine ratio at the age of 8 weeks which was partly reversible by a 4-week treatment with Ramipril (Figure 1).
Figure 1: Quantification of UACR in urine samples. Urine albumin-creatinine ratio measured in urine samples collected at the age of 4 and 8 weeks. Two-way ANOVA with Bonferroni’s post hoc test. n = 12 per group. Mean ± SEM; ***p <0.001.
Col4A3-/- mice present increased blood urea nitrogen levels in the plasma at the age of 8 weeks. Treatment with Ramipril was able to slightly reduce blood urea nitrogen levels after 4 weeks of treatment (Figure 2B).
Figure 2: Quantification of blood urea nitrogen (BUN) in the plasma. BUN measured in plasma samples collected at treatment start (week 4) and 4 weeks after treatment start (week 8). One-way ANOVA with Kruskal-Wallis post hoc test. n = 12 per group. Mean ± SEM; ***p <0.001.
Scantox 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:
- Urine albumin-creatinine ratio
- Blood urea nitrogen
- Renal smooth muscle actin
- Renal periodic acid–schiff (PAS)
- Blood levels
- Ability to urinate
- Survival
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Scantox is ready to provide samples (e. g. kidney) from Col4a3-/- mice for analyses in your laboratory.
