Animal models of inherited metabolic diseases : proceedings of the International Symposium on Animal Models of Inherited Metabolic Disease held in Bethesda, Maryland, October 19-20, 1981 / editors: Robert J. Desnick, Donald F. Patterson, Dante G. Scarpelli.
- International Symposium on Animal Models of Inherited Metabolic Disease (1981 : Bethesda, Md.)
- Date:
- [1982]
Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Credit: Animal models of inherited metabolic diseases : proceedings of the International Symposium on Animal Models of Inherited Metabolic Disease held in Bethesda, Maryland, October 19-20, 1981 / editors: Robert J. Desnick, Donald F. Patterson, Dante G. Scarpelli. Source: Wellcome Collection.
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![defects with residual activities which permit further comparison of their mutations with those in the human diseases. Interestingly, residual activities occur in both the human and animal counterparts of the following dis orders: mannosidosis, G M1 ~gangliosidosis and mucopoly saccharidosi s Type VI. Comparison of the kinetic, physical and immunologic properties of these defective enzymes revealed that none of these animal models were homologues, but rather, were analogues of their human disease counter parts. These studies are summarized in Table 2 and are discussed below. cx-Mannosidosis . The residual a-mannosidase activities in both the bovine and human disorders had increased K values, decreased thermostabilities and cross-reacted witW antibodies to the respective normal enzymes, consistent with a structural gene mutation (Burditt et a]_., 1978). The only difference between the human and bovine residual enzymes was the amount of activity detected 2-8% vs. ~ 15% of normal, respectively). In contrast, the residual activity in feline mannosidosis was only 2% of normal levels and had similar physical and kinetic properties to the normal feline enzyme (Burditt et_ al_., 1980). Although the immunologic properties of the residual feline enzyme were not investigated, it was suggested that the residual activity was the result of a structural gene mutation that led to enhanced susceptibility of the enzyme to proteolysis or an alteration in some property which decreased catalytic activity; a regulatory gene mutation, although less likely, was also considered (Burditt ejt al_., 1980). Further puri fication and characterization, including CRM studies, are required to discriminate among these possibilities. GMi -Gangliosidosis . The feline model of G^-ganglio- sidosTs has 10% residual hepatic activity which has an altered K toward both the natural and artificial sub strates, i? thermolabile, migrates less anodally and is not recognized (CRM-negative) by the antibody raised against normal feline p-galactosidase (Holmes and O'Brien, 1978). In contrast, the canine enzyme has 1% of normal hepatic activity, normal kinetic and physical properties and an amount of CRM directly corresponding to the amount of activity (Rittmann et_ al_., 1980). Thus, the feline muta tion is consistent with a structural gene mutation, but the nature of the canine mutation is unclear; possible muta tions include mRNA processing, regulatory gene as well as](https://iiif.wellcomecollection.org/image/b18027842_0067.JP2/full/800%2C/0/default.jpg)
