Interest in using caprine beta-D-
mannosidosis as a model to evaluate
bone marrow transplantation in the treatment of human lysosomal storage disorders provided the stimulus for characterization of
beta-D-mannosidase in selected goat tissues and induction of hemopoietic chimerism in the goat. Total
beta-D-mannosidase activity was measured with the use of 4-methylumbelliferyl beta-D-
mannopyranoside as substrate. Residual activity in mutant liver was 52% of control but no activity was detectable in mutant kidney or brain tissue. Normal adult goat liver contained two forms of
beta-D-mannosidase, a nonlysosomal form (52%) with a broad pH range for optimum activity (4.5-8.0) and a lysosomal form (48%) with a pH optimum of 5.5. Residual
enzyme in mutant liver consisted entirely of the nonlysosomal form. Normal adult thyroid, kidney and brain contained two major lysosomal
isoenzymes with pIs 5.5 and 5.9 and traces of a minor
isoenzyme with pI 5.0. Normal liver contained three
isoenzymes with similar pIs; however, an
isoenzyme with pI 5.0 predominated. In 60-day fetal liver lysosomal
isoenzymes predominated and only trace amounts of nonlysosomal
isoenzyme were detectable. Total hepatic
beta-D-mannosidase activity increased towards adult levels during the last 90 days of gestation as a result of increasing nonlysosomal
isoenzyme activity.
Intraperitoneal injection of fetal liver cells into 60-day goat fetuses resulted in sustained hemopoietic chimerism in surviving kids without evidence of
graft-versus-host-disease. These results suggest that
transplantation of normal fetal liver cells into preimmunocompetent goat fetuses affected with beta-D-
mannosidosis is feasible and may provide an alternative strategy for evaluation of postnatal
bone marrow transplantation in the treatment of human lysosomal storage disorders.