Quick Summary
Phenotype: Affected dogs typically present with vision loss, head tremors, walking and balance issues, and weight loss by 6 months of age. The disease is progressive and lethal by 18 months.
Mode of Inheritance: Autosomal recessive
Alleles: N = Normal, G = GM1 gangliosidosis
Breeds appropriate for testing: Shiba Inu
Explanation of Results:
- Dogs with N/N genotype will not have GM1 gangliosidosis and cannot transmit this variant to their offspring.
- Dogs with N/G genotype will not be affected by GM1 gangliosidosis, but are carriers. They will transmit this variant to 50% of their offspring. Matings between two carriers are predicted to produce 25% GM1 gangliosidosis-affected puppies.
- Dogs with G/G genotype are expected to develop GM1 gangliosidosis, a lethal disorder.
Results of this test can be submitted to the OFA (Orthopedic Foundation for Animals)
GM1 gangliosidosis in the Shiba Inu breed (SI-GM1) is a hereditary lysosomal storage disorder caused by abnormal accumulation of GM1 ganglioside, a fatty molecule (lipid) important for normal functioning of nerve cells in the brain. Affected dogs typically present with vision loss, head tremors, walking and balance issues, and weight loss by 6 months of age. The disease is progressive and lethal by 18 months.
SI-GM1 results from the loss of a nucleotide (c.1668delC) in the b-galactosidase gene, which codes for the beta-galactosidase enzyme. The deletion causes a change in the last 15% of the beta-galactosidase enzyme that renders it dysfunctional. In nerve cells, beta-galactosidase is found in the lysosomes, vesicles inside the cells that break down and recycle molecules. In dogs with defective beta-galactosidase, accumulation of GM1 gangliosides leads to progressive damage of nerve cells of the brain and central nervous tissue.
SI-GM1 is inherited in an autosomal recessive fashion, which means that males and females are equally affected and that two copies of the defective gene are needed to cause the disease. Dogs with one normal and one affected gene (carriers) are normal and show no sign of the disease.
This mutation has not been identified in other breeds with GM1 gangliosidosis and is different from the mutation identified in Portuguese Waterdogs. Genetic testing assists veterinarians with diagnosis of SI-GM1 and helps breeders to identify carriers to avoid breeding these together.
Species
Breed
Type of Test
| Test Result | GM1 Gangliosidosis |
|---|---|
| N/N | Normal. No copies of the SI-GM1 mutation. |
| N/G | Carrier. 1 copy of the SI-GM1 mutation. Dog is normal. |
| G/G | Affected. 2 copies of the SI-GM1 mutation. Dog will develop GM1 gangliosidosis. |
Yamato, O., Endoh, D., Kobayashi, A., Masuoka, Y., Yonemura, M., Hatakeyama, A., Satoh, H., Tajima, M., Yamasaki, M. & Maede, Y. (2002). A novel mutation in the gene for canine acid b-galactosidase that causes GM1-gangliosidosis in Shiba dogs. Journal of Inherited Metabolic Disease, 25, 525-526. doi: 10.1023/A:1021280007739
