Document Detail


Inheritance, biochemical abnormalities, and clinical features of feline mucolipidosis II: the first animal model of human I-cell disease.
MedLine Citation:
PMID:  14557388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Mazrier; M Van Hoeven; P Wang; V W Knox; G D Aguirre; E Holt; S P Wiemelt; M M Sleeper; M Hubler; M E Haskins; U Giger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of heredity     Volume:  94     ISSN:  0022-1503     ISO Abbreviation:  J. Hered.     Publication Date:    2003 Sep-Oct
Date Detail:
Created Date:  2003-10-14     Completed Date:  2004-06-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375373     Medline TA:  J Hered     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-73     Citation Subset:  IM    
Affiliation:
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6010, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cats
Disease Models, Animal*
Female
Humans
Lysosomal Storage Diseases / genetics,  metabolism,  physiopathology
Male
Mucolipidoses / genetics*,  metabolism,  physiopathology
Pedigree
Retina / pathology
Time Factors
Grant Support
ID/Acronym/Agency:
EY-13132/EY/NEI NIH HHS; RR 02512/RR/NCRR NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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