Normal lysosomal morphology and function in LAMP-1-deficient mice

Lysosomal membranes contain two highly glycosylated proteins, designated LA MP-1 and LAMP-2, as major components. LAMP-1 and LAMP-S are structurally re lated, To investigate the physiological role of LAMP-1, we have generated m ice deficient for this protein. LAMP-l-deficient mice are viable and fertil e. In LAMP-1-deficient brain, a mild regional astrogliosis and altered immu noreactivity against cathepsin-D was observed. Histological and ultrastruct ural analyses of all other tissues did not reveal abnormalities. Lysosomal properties, such as enzyme activities, lysosomal pH, osmotic stability, den sity, shape, and subcellular distribution were not changed in comparison wi th controls. Western blot analyses of LAMP-1-deficient and heterozygote tis sues revealed an up-regulation of the LAR IP-S protein pointing to a compen satory effect of LAMP-S in response to the LAMP-1 deficiency. The increase of LAMP-2 was neither correlated with an increase in the level of lamp-2 mR NAs nor with increased half-life time of LAMP-2, This findings suggest a tr anslational regulation of LAMP-2 expression.