Biochemical Genetics

, Volume 25, Issue 1–2, pp 161–174 | Cite as

Abnormal subcellular distribution of β-glucuronidase in mice with a genetic alteration in enzyme structure

  • Richard T. Swank
  • Karen Moore
  • Verne M. Chapman


Liver β-glucuronidase is structurally altered in inbred strain PAC so that a peptide subunit with a more basic isoelectric point, GUS-SN, is produced. This allele of β-glucuronidase was transferred to strain C57BL/6J by 12 backcross matings to form the congenic line B6 · PAC-Gusn. Liver β-glucuronidase activity was halved in males of the congenic strain compared to normal males. The lowered activity was specifically accounted for by a decrease in the lysosomal component. There was no alteration in the concentration of microsomal activity. This alteration in the subcellular distribution of β-glucuronidase in Gusn/Gusn mice was confirmed by two independent gel electrophoretic systems which separate microsomal and lysosomal components. β-Glucuronidase activity was likewise approximately halved in mutant spleen, lung, and brain, organs which contain exclusively or predominantly lysosomal β-glucuronidase. The loss of liver lysosomal β-glucuronidase activity was shown by immunotitration to be due to a decrease in the number of β-glucuronidase molecules in lysosomes of the congenic strain. The Gusn structural alteration likely causes the lowered lysosomal β-glucuronidase activity since the two traits remain in congenic animals. Heterozygous Gusn/Gusb animals had intermediate levels of liver β-glucuronidase. Also, the effect was specific, in that three other lysosomal enzymes were not reproducibly lower in Gusn/Gusn mice. Gusn is, therefore, an unusual example of a mutation which causes a change in the subcellular distribution of a two-site enzyme.

Key words

β-glucuronidase lysosomal microsomal subcellular congenic 


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Copyright information

© Plenum Publishing Corporation 1987

Authors and Affiliations

  • Richard T. Swank
    • 1
  • Karen Moore
    • 2
  • Verne M. Chapman
    • 1
  1. 1.Department of Molecular BiologyRoswell Park Memorial InstituteBuffalo
  2. 2.Frederick Cancer Research FacilityFrederick

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