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 (Mochizuki et al. 1994; Colville et al. 1997). Patients with Alport syndrome were reported to show mutations in collagen IV genes (Mochizuki et al.1994; Lemmink et al. 1994 and 1997; Gubler et al. 1995).
Mice homozygous for the Col4A3-/- targeted mutation are a model of autosomal-recessive Alport syndrome (Cosgrove et al. 2007). Animals bred on a 129/SvJ background develop glomerulonephritis and die at about 8.5 week of age (Jackson Laboratory strain: #002908). Animals have a mean survival of 10 weeks. Col4A3-/- mice have 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 albumine levels in the urine of Col4A3-/- mice showed highly increased albumine levels in Col4A3-/- mice 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.
Since homozygous Col4a3-/- mice reflect key features of Alport syndrome, this mouse model is useful to test potential drug candidates.
Typical analysis parameters are:
- Renal Smooth muscle actin
- Renal Periodic acid–Schiff (PAS) staining for polysaccharides
- Blood analyses
- Ability to urinate
QPS Neuropharmacology is ready to provide samples (brain tissue, CSF etc.) from these animals for analyses in your laboratory.