Improved GUSB activity and GAG levels, and corrected tissue pathology by BMT after poly(I:C) and 5-FU preconditioning. Eight-week-old Sly mice were untreated (n = 4) or treated with either 5-FU alone (n = 5) or poly(I:C) and 5-FU (n = 6), and were then given 1 × 10⁷ of whole BM cells from littermate WT mice. (A) Spleen sections prepared from 5-month-old Sly, WT, or BMT mice (3 months after BMT), stained for GUSB activity (red) and counterstained with methyl green. Original magnification, ×40. The blood chimerism (GUSB⁺ cell percentage) in the recipient Sly mice shown here was as follows: none: 0.38% in B cells, 0.87% in T cells, and 1.99% in myeloid cells; 5-FU: 0.69% in B cells, 0.98% in T cells, and 3.62% in myeloid cells; poly(I:C) plus 5-FU conditioning: 10.1% in B cells, 14.2% in T cells, and 6.44% in myeloid cells. (B) Liver (left) and spleen (right) sections, stained with toluidine blue, taken from 5-month-old WT or Sly mice, or from Sly mice preconditioned with poly(I:C), and 5-FU followed by BMT (2 examples, representative of 6 mice). Samples from BMT mice were taken 3 months after BMT. Lysosomes distended by abnormal storage material appear as clear, foamy areas by this method. Bar represents 100 μm. (C) GUSB activity in spleen (left) and liver (right) homogenates from BMT mice (3 months after BMT) was determined by fluorometric assay. GUSB activity is expressed as nmol/hr/mg protein. (D) The levels of CS and dermatin sulfate in spleen homogenates from BMT mice (at 3 months after BMT) were measured as described in “Methods.” GAG level is expressed as ng/mg wet tissue. Horizontal bars show the average percentage for each group. Each symbol represents an individual mouse. Combined data from 6 independent experiments are shown (C, D). *P < .05; **P < .01; ***P < .001. ns, not significant.