Cystinosis Mouse and Rat Models

Experiments were conducted on age- and gender-matched Ctns knockout mouse (C57BL/6 background^{4 (link)}) or rat (Sprague-Dawley background^{22 (link)}) lines, and their corresponding control littermates. Due to an effect of sex on cystine content (higher levels in female versus male kidneys mice^{5 (link),15 (link),43 (link)}), only female mice at age 6, 12, and 24 weeks were used for primary cell cultures and mechanistic studies. Rats and mice were housed under specific pathogen free conditions and maintained under temperature (22–25 °C)- and humidity (50–60%)-controlled conditions with 12-h dark/light cycle with water and food provided ad libitum. Kidneys were collected for analyses at the time of sacrifice. Both male and female rats aged 12 weeks were subcutaneously implanted with a slow-release pellet (Innovative Research of America, FL, USA). The pellets were designed to allow a constant release of rapamycin (1.5 mg/kg B.W./day; R-5000, LC Laboratories, Woburn, MA). Control animals received a placebo pellet equivalent to their respective rapamycin-treated group. After 2 weeks of treatment, the rats were sacrificed, and the kidney tissues were harvested and collected for subsequent analyses.