Introduction

GM1 gangliosidosis is a fatal, progressive, neurodegenerative lysosomal storage disease caused by mutations in the β-galactosidase (GLB1) gene. In feline GM1 gangliosidosis, a pathogenic mutation (c. 1448G > C) has been identified in the feline GLB1 gene and it has been found in Siamese, Korat and mixed-breed cats in several countries including Japan. Recently, two different families of feline GM1 gangliosidosis caused by each different novel mutation were found in Japanese domestic shorthair cats.

Objectives

To identify novel pathogenic mutations of the feline GLB1 gene.

Methods

Direct-sequence analysis and RT-PCR were performed to identify the causative mutation using genomic DNA and total RNA samples collected from affected, carrier and normal cats. The genotyping survey was carried out in the cat population in Japan using real-time PCR methods.

Results

Two novel pathogenic mutations in the feline GLB1 gene were identified in the different pedigrees of Japanese domestic shorthair cats. The genotyping survey revealed those two mutant alleles are not present in the population of about 1000 unaffected cats.

Conclusion

In this study, we successfully identified the two novel pathogenic mutations in feline GM1 gangliosidosis. The disease caused by these novel mutations will be very important not only in feline veterinary medicine but also as an animal model for the human disease.