I-cell disease-like phenotype in mice deficient in mannose 6-phosphate receptors

Mannose 6-phosphate receptor deficient mice were generated by crossing mice carrying null alleles for Igf2 and the 300 kDa and 46 kDa mannose 6-phosph ate receptors, Mpr300 and Mpr46. Pre- and perinatal lethality of mice nulli zygous for Igf2, Mpr300 and Mpr46 was increased. Triple deficient mice surv iving the first postnatal day had normal viability and developed a phenotyp e resembling human I-cell disease. The triple deficient mice were character ized by dwarfism, facial dysplasia, waddling gait, dysostosis multiplex, el evated lysosomal enzymes in serum and histological signs of lysosomal stora ge predominantly in fibroblasts, but also in parenchymal cells of brain and liver. A paternally inherited Mpr300 wild type allele that is normally ina ctive in mice due to imprinting was reactivated in some tissues of mice lac king IGF II and MPR 46 and carrying a maternal Mpr300 null allele. Inspite of the partial reactivation the phenotype of these mice was similar to that of triple deficient mice.