Figure 1.

Cat L–deficient mice are protected from pancreatic insulitis. (A) Diabetes frequency was determined by measurement of urine glucose levels in Cat L–deficient (Cat L^–/–, open squares, n = 13), Cat L–heterozygous (Cat L^+/–, open circles, n = 23), and Cat L–wild-type (Cat L^+/+, filled squares, n = 9) female NOD mice. *Statistical analysis by the χ² test yielded a value of P < 0.001 for diabetes incidence in 29-week-old Cat L–deficient compared with wild-type NOD mice. (B) At 10–11 weeks of age, Cat L–deficient mice (–/–) together with control wild-type (+/+) and heterozygous (+/–) littermates were analyzed for insulitis by scoring histological analysis. Insulitis was characterized as peri-, nonextensive, or extensive depending on the level of infiltration. Peri-insulitis is reflected as a noninvasive leukocyte accumulation outside the pancreatic islet whereas nonextensive insulitis describes an invasive infiltrate in the pancreatic islet. In extensive insulitis, more than 50% of the individual pancreatic islet is infiltrated or destroyed. Each bar represents an individual mouse. (C and D) At 14–19 weeks of age, male and female Cat L–deficient animals and control littermates were analyzed for infiltration of the pancreas. (E) Levels of insulitis present in 23- to 38-week-old Cat L–deficient NOD mice and control littermates were determined. Mice examined in the 23- to 38-week age groups were female except for 2 Cat L–deficient male NOD mice.