Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats

Edward Neuwelt, W. G. Johnson, N. K. Blank, M. A. Pagel, C. Maslen-McClure, M. J. McClure, P. M. Wu

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Abstract

We have detected a disorder in Korat cats (initially imported from Thailand) that is analogous to human Sandhoff's disease. Pedigree analysis indicates that this disease in an autosomal recessive disorder in the American Korat. Postmortem studies on one affected cat showed hepatomegaly that was not reported in the only other known feline model of G(M2)-gangliosidosis type II. Histologic and ultrastructural evaluation revealed typical storage vacuoles. There was a marked deficiency in the activity of hexosaminidase (HEX) A and B in affected brain and liver as compared to controls. Electrophoresis of a liver extract revealed a deficiency of normal HEX A and B in the affected animals. The blocking primary enzyme immunoassay verified the presence of antigenically reactive HEX present in affected cat livers in quantities slightly elevated with respect to the normal HEX concentration in control cats. In leukocytes, obligate heterozygotes had intermediate levels of total HEX activity with a slight increase in the percent activity due to HEX A. Indeed, 4 of 11 phenotypically normal animals in addition to four obligate heterozygotes appear to be carriers using this assay. Affected brain and liver compared with control brain and liver contained a great excess of bound N-acetylneuraminic acid in the Folch upper-phase solids; thin-layer chromatography showed a marked increase in G(M2)-ganglioside. In summary, we have characterized the pedigree, pathology, and biochemistry of a new feline model of G(M2)-gangliosidosis which is similar to but different from the only other known feline model.

Original languageEnglish (US)
Pages (from-to)482-490
Number of pages9
JournalJournal of Clinical Investigation
Volume76
Issue number2
StatePublished - 1985

Fingerprint

GM2 Gangliosidosis
Sandhoff Disease
Hexosaminidases
Felidae
Cats
Hexosaminidase A
Liver
Pedigree
Heterozygote
Brain
Hexosaminidase B
G(M2) Ganglioside
Liver Extracts
Hepatomegaly
N-Acetylneuraminic Acid
Thailand
Thin Layer Chromatography
Vacuoles
Immunoenzyme Techniques
Biochemistry

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Neuwelt, E., Johnson, W. G., Blank, N. K., Pagel, M. A., Maslen-McClure, C., McClure, M. J., & Wu, P. M. (1985). Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats. Journal of Clinical Investigation, 76(2), 482-490.

Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats. / Neuwelt, Edward; Johnson, W. G.; Blank, N. K.; Pagel, M. A.; Maslen-McClure, C.; McClure, M. J.; Wu, P. M.

In: Journal of Clinical Investigation, Vol. 76, No. 2, 1985, p. 482-490.

Research output: Contribution to journalArticle

Neuwelt, E, Johnson, WG, Blank, NK, Pagel, MA, Maslen-McClure, C, McClure, MJ & Wu, PM 1985, 'Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats', Journal of Clinical Investigation, vol. 76, no. 2, pp. 482-490.
Neuwelt E, Johnson WG, Blank NK, Pagel MA, Maslen-McClure C, McClure MJ et al. Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats. Journal of Clinical Investigation. 1985;76(2):482-490.
Neuwelt, Edward ; Johnson, W. G. ; Blank, N. K. ; Pagel, M. A. ; Maslen-McClure, C. ; McClure, M. J. ; Wu, P. M. / Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats. In: Journal of Clinical Investigation. 1985 ; Vol. 76, No. 2. pp. 482-490.
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