A complex rearrangement in GBE1 causes both perinatal hypoglycemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats
Section snippets
Animals
We established a feline GSD IV breeding colony by mating a carrier male NFC (cat A in Fig. 1) to an unrelated female domestic shorthair cat (cat B in Fig. 1). Matings were performed by placing females housed under 16 h of light/day in a room occupied by a specific male until pregnancy could be detected by abdominal palpation. Deliveries generally occurred unobserved and unaided during nighttime hours. We performed all matings, specimen collection, determination of clinical phenotype, and
Breeding experiments
We identified a purebred NFC male as a carrier of GSD IV by measurement of approximately half-normal GBE activity in peripheral blood leukocytes and liver (cat A in Fig. 1). A breeding colony was established by mating this cat with an unrelated healthy domestic shorthair cat of known lineage (cat B in Fig. 1). GBE activity was measured in leukocytes of offspring from 4 litters produced by this mating, and females considered to have half-normal activity were raised for matings with the
Discussion
In humans, the age of onset, organ distribution, and clinical course of GSD IV is highly variable, ranging from mild nonprogressive hepatopathy to fetal neuromuscular dysfunction and immediate-postnatal cardiopulmonary collapse [4]. This clinical heterogeneity has been attributed to differing GBE1 mutations that, in turn, are presumed to provide varied amounts of residual enzyme activity, albeit the available assays for GBE activity measurement are imprecise at lower activities and vary between
Acknowledgments
This work was supported by the NIH Referral Center—Animal Models of Human Genetic Disease (RR02512) at the University of Pennsylvania School of Veterinary Medicine and the Genetics Research Fund of the Michigan State University College of Veterinary Medicine. We thank Adam Seng and Polly Foureman, DVM, for DNA testing of privately owned cats, and Barry Prior, currently of the Department of Veterinary Biomedical Sciences, University of Missouri, Columbia, for the muscle nuclear magnetic
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- 1
Present address: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
- 2
Present address: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.