How is GM1 Gangliosidosis (Discovered in the Shiba) inherited in dogs?

GM1 Gangliosidosis (Discovered in the Shiba) follows a Autosomal recessive inheritance pattern. It has been observed in 2 of 266 breeds screened in the Sniff Atlas.

What is the human equivalent of GM1 Gangliosidosis (Discovered in the Shiba)?

OMIA links GM1 Gangliosidosis (Discovered in the Shiba) to its human counterpart in OMIM (OMIM 230500, OMIM 230600, OMIM 230650, OMIM 253010), the bridge to the deeper human-medicine literature for the same underlying biology.

How well studied is GM1 Gangliosidosis (Discovered in the Shiba) in dogs?

OMIA curates 44 peer-reviewed references for GM1 Gangliosidosis (Discovered in the Shiba). The full, linked citation list is on this page.

Canine Mendelian disease record

GM1 Gangliosidosis (Discovered in the Shiba)

GM1 Gangliosidosis (Discovered in the Shiba). Autosomal recessive. Observed in 2 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier: OMIA:000402-9615
Inheritance: Autosomal recessive
Source dataset: Sniff Atlas v1.0.1 / DOI

The human connection

A model of human GM1 gangliosidosis type 1

Dogs with this condition carry a change in GLB1. In people, changes in the same gene cause GM1 gangliosidosis type 1. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: GM1 gangliosidosis type 1 is the severe infantile form of GM1 gangliosidosis with variable neurological and systemic manifestations.

In humans it is also called: Beta galactosidase deficiency type 1, gangliosidosis generalized GM1 infantile form, gangliosidosis generalized GM1 type 1, GLB deficiency type 1, infantile GM1 gangliosidosis.

MONDO:0009260 OMIM 230500 OMIM 230600

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Closely related human conditions exist for this gene. Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

GM1 gangliosidosis is a lysosomal storage disease caused by beta galactosidase deficiency and characterized by progressive neurological deterioration. It is caused by mutations in GLB1, although the mutations differ by breed. There is a genetic test available.

Clinical features

Affected dogs generally have proportional dwarfism, which is easily observed in the Alaskan husky, and all develop progressive cerebellar dysfunction and limb weakness. Signs include weight loss, ataxia, wide-based gait, decreased proprioception, intention tremor of the head, ataxia, hypermetria, dysmetria, internal strabismus, and positional nystagmus. Signs begin around 6 to 8 weeks of age, and are clearly noticeable by 7 months of age. Abnormal endochondral ossification of vertebral epiphyses was visible in radiographs of 5.5 month old affected Alaskan huskies. Affected dogs occasionally have an increase in serum ALP. Coarse facial features are seen in affected English springer spaniels (Müller et al., 2001, Alroy et al., 1992). Bone marrow transplantation therapy was attempted but ineffective in affected Portugese water dogs (O’Brien et al., 1990).

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Wang et al. (2000) showed that the causative mutation in Portuguese water dogs is a G to A transition in exon 2 of the GLB1 gene, that causes an amino acid change from arginine to histidine in the resultant peptide. The causative mutation in Shiba dogs is a deletion of a cytosine in exon 15 that causes a premature stop codon in GLB1 (Yamato et al., 2002). The causative mutation in Alaskan huskies is a 19 base pair duplication in exon 15 that variably disrupts mRNA splicing and result in no functional GLB1 (Kreutzer et al., 2005).

Pathology

Affected dogs are deficient in acid beta-galactosidase and are unable to completely degrade complex oligosaccharides. The result is lysosomal accumulation of GM1 gangliosides and other galactose-containing glycoconjugates with a nonreduced terminal beta-galactosidic linkage (Müller et al., 2001). On histologic examination, most neurons in the central nervous system contain densely packed, PAS positive cytoplasmic inclusions, giving the appearance of foamy or granular cytoplasm. Other changes include mild demyelination, axonal degeneration, significant astrogliosis, and significant loss of oligodendrocytes (Müller et al., 2001). Vacuoles are also found in hepatocytes and renal tubular epithelial cells (Shell et al 1989).

Prevalence

The frequency of heterozygotes in normal (unaffected) Shiba Inu dogs in Japan has been reported by Yamato et al. (2008) as 2/68 (2.94%) and by Uddin et al. (2013) as 6/590 (1.02%). In unaffected miniature Shibu Inu (called Mame Shiba), Pervin et al. (2022) reported a heterozygote frequency of 9/1832 (= 0.49%).

Control

Relatives of affected dogs should be tested and breeding of affected or carrier dogs should be avoided.

Genetic testing

There are tests available to detect the known causative mutations.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 230500 Disease · OMIM 230600 Disease · OMIM 230650 Disease · OMIM 253010 Gene · OMIM 611458

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000402-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 44.

Development of small-molecule allosteric modulators of beta-galactosidase (β-Gal) for the treatment of GM1 gangliosidosis and Morquio B. · Int J Mol Sci · 2026 · PMID 42074270
An overview of canine inherited neurological disorders with known causal variants. · Animals (Basel) · 2023 · PMID 38003185
Phenotypic and genetic aspects of hereditary ataxia in dogs. · J Vet Intern Med · 2023 · PMID 37341581
Validation of a highly sensitive HaloTag-based assay to evaluate the potency of a novel class of allosteric β-Galactosidase correctors. · PLoS One · 2023 · PMID 38019733
Carrier rate and mutant allele frequency of GM1 gangliosidosis in miniature Shiba Inus (Mame Shiba): Population screening of breeding dogs in Japan. · Animals (Basel) · 2022 · PMID 35625088
In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses. · BMC Vet Res · 2016 · PMID 27036194

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for GM1 Gangliosidosis (Discovered in the Shiba) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A

Parent B

NNClear

NmCarrier

mmAffected

Clear25%

Carrier50%

Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.

Your breed

See what GM1 Gangliosidosis (Discovered in the Shiba) looks like in your dog's breed.

Carrier frequency by breed

Top 2 well-sampled breeds (n ≥ 50)

Maximum carrier frequency per breed across variants in the Donner 2023 cohort, with Wilson 95% confidence intervals. The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%1%2%

Portuguese Water Dog0.15% · n 664

0.15%n 664

Japanese Shiba Inu<0.1% · n 2,123

<0.1%n 2,123

n = 2,787 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas

Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for GM1 Gangliosidosis (Discovered in the Shiba) is measured; phenotype outcome depends on penetrance and modifiers.

▸ Full table with Wilson 95% confidence intervals

Breed	Carrier frequency	Wilson 95% CI	n tested
Portuguese Water Dog	0.15%	[0.0%, 0.8%]	664
Japanese Shiba Inu	<0.1%	[0.0%, 0.3%]	2,123

264 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

Sniff Atlas v1.0.1 for the per-breed carrier frequencies:
Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.
OMIA for the disease definition, inheritance, and gene assignment:
Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:000402-9615.
Donner et al. 2023 for the breed × variant carrier-frequency cohort:
Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Sniff Atlas v1.0.1, the source dataset for these frequencies.
Browse breeds, per-breed Mendelian profiles, including this disease in context.
OMIA entry OMIA:000402-9615, authoritative clinical reference.
About OMIA, the catalogue this record comes from, and how Sniff uses it.

Last updated June 20, 2026

Sources: Sniff Atlas v1.0.1 · OMIA OMIA:000402-9615 · Donner et al. 2023