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. 2015 Sep 19;2(11):987–1001. doi: 10.1002/acn3.245

Figure 1.

Figure 1

Transgenic alpha‐mannosidase knockout mice express inactive human LAMAN and are immune‐tolerant. (A) Repeated injections every other week of recombinant human LAMAN with doses of 25 and 500 U/kg into the tail vein of nontransgenic alpha‐mannosidase knockout mice (‐/‐) leads to premature death during 16 weeks of treatment whereas mock‐injected mice (‐/‐ PBS) were not affected. (B) Immunoblot analyses of tissue lysates revealed transgene driven expression of inactive human LAMAN in brain and spleen of transgenic 14 knockout mice (‐/‐ +tg) but not in nontransgenic wild‐type (+/+) and knockout (‐/‐) tissue. LAMAN‐specific bands detected at about 130, 70 and 14 kDa correspond to the precursor (p) and lysosomal processed forms (m) of LAMAN. (C) Transgenic expression of LAMAN throughout the central nervous system including cerebellum, hippocampus and cortex as determined by 3,3'‐Diaminobenzidine (DAB)‐immunohistochemistry, using a LAMAN‐specific antibody (Scale bars = 500 μm). (D) alpha‐mannosidase activity of brain and spleen homogenates indicates lack of enzymatic activity in both knockout mouse strains. (E) The antibody (LAMAN‐specific IgG) response in plasma of transgenic knockout mice compared to nontransgenic animals is reduced as determined by an ELISA after seven weekly injections of 500 U/kg (*P < 0.05). LAMAN, lysosomal acid alpha‐mannosidase; PBS, phosphate‐buffered saline; ELISA, enzyme‐linked immunosorbent assay.