Journal of Heredity 2003:94(5)
© 2003 The American Genetic Association 94:363-373
Inheritance, Biochemical Abnormalities, and Clinical Features of Feline Mucolipidosis II: The First Animal Model of Human I-Cell Disease
From the Departments of Clinical Studies (Mazrier, Van Hoeven, Wang, Knox, Holt, Wiemelt, Sleeper, Haskins, and Giger) and Pathobiology (Haskins), School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6010; Baker Institute, College of Veterinary Medicine, Cornell University, Ithaca, NY (Aguirre); and Department of Reproduction, Faculty of Veterinary Medicine, University of Zürich, Zürich, Switzerland (Hubler).
Address correspondence to Urs Giger, Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey St., Philadelphia PA 19104-6010, or e-mail: giger{at}mail.vet.upenn.edu.
Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats with ML II that was established from a half-sibling male of an affected cat. Ten male and 9 female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal enzymes from affected kittens, compared to normal adult control cats, were high in serum (11–73 times normal) but low in cultured fibroblasts (9–56% of normal range) that contained inclusion bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme activities of adult obligate carriers were intermediate between normal and affected values. Clinical features in affected kittens were observed from birth and included failure to thrive, behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All clinical signs were progressive and euthanasia or death invariably occurred within the first few days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous with ML II in humans. Feline ML II is currently the only animal model in which to study the pathogenesis of and therapeutic interventions for this unique storage disease.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. M. Gelfman, P. Vogel, T. M. Issa, C. A. Turner, W.-S. Lee, S. Kornfeld, and D. S. Rice Mice Lacking {alpha}/{beta} Subunits of GlcNAc-1-Phosphotransferase Exhibit Growth Retardation, Retinal Degeneration, and Secretory Cell Lesions Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5221 - 5228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-S. Lee, B. J. Payne, C. M. Gelfman, P. Vogel, and S. Kornfeld Murine UDP-GlcNAc:Lysosomal Enzyme N-Acetylglucosamine-1-phosphotransferase Lacking the {gamma}-Subunit Retains Substantial Activity toward Acid Hydrolases J. Biol. Chem., September 14, 2007; 282(37): 27198 - 27203. [Abstract] [Full Text] [PDF]
|
|