Mice homozygous for this Ctsl targeted mutation are viable, normal in size, and do not display any behavioral abnormalities. Western blot analysis failed to detect any signal in kidneys of homozygous mutant mice. No Ctsl enzymatic activity was detected in the kidney using a synthetic substrate. Donating investigator reports that homozygous females are infertile; while homozygous males breed well. As reported in the B6-Ctsltm1Cptr by Roth et al. 2000, the vibrissae of NOD congenic mutant mice have not penetrated the epidermis at birth and the first emergence of fur is delayed by approximately two days. Beginning around three weeks of age NOD mutant mice begin to lose their fur beginning at the head and progressing toward the tail region. Mature mutant mice are always partially devoid of fur. Unlike the observations of Roth et al. there appears to be no distortion of the the expected rates of homozygous NOD congenic mice weaned. Similar to Maehr et al. 2005, no throiditis, sialadenitis, diabetes or insulitis was detected in NOD.Ctsl deficient females aged to 10 months (Hsing et al, 2009). Ctsl deficient mice exhibit defective CD4+T cell development leading to a reduced CD4:CD8 ratio. CD4+T cells if naive NOD.Ctsl deficient mice exhibit Foxp3 expression at 2 fold higher frequency than wildtype controls (Hsing et al, 2009).
This model provides a tool for detailed studies to identify the molecular pathways of major lysosomal cysteine proteases, specifically cathepsin L in immune modulation.
