Shiba inu specialized breeder ◈ Awa-shi Tokushima Japan

A genetic disease of Shiba dogs (GM1 gangliosidosis)

Osamu Yamato
Professor of Joint Faculty of Veterinary Medicine, Kagoshima University


When genetic information (DNAstrong>) in a cell nucleus is copied at cell division, a mutation may occur at a very low probability. When mutation takes place during the process of producing generative cells (sperms and ova), it may cause genetic diseases and the mutation may be inherited to the offspring. However, as offspring inherits sets of genetic information from the father and mother, respectively, at the same amount (making pairs of genes), when a mutation occurs in only one of the pair, there is no onset of a disease but when it occurs in both of the pair, there is an onset of a disease. This kind of genetic diseases are called recessive hereditary diseases. In a word, recessive hereditary diseases are manifested only when the same causal mutation of a disease is inherited from both the mother and father.

When both the father and mother have only one same mutation (these individuals are called “carrier” and healthy like a normal individual), by crossing the two carrier dogs, one onset individual, which would have a disease, is born at a probability rate of 1/4 (25%). As you see Figure 1A, the probability is that one onset individual, two carriers and one normal individual would be born by crossing two carries (if four babies are born). The probability of having a male onset individual and that of having a female onset individual are the same. In addition, as Figure B below shows, when one parent is a carrier and the other is a normal one, no onset dog would be born but half of the baby dogs would be carriers. Obviously, as shown in Figure 1C, when both parents are normal, all the baby dogs are normal.

Crossing patterns regarding gene tic diseases
Figure 1. Crossing patterns regarding genetic diseases

In the natural probability distributions, a crossing pattern shown in 1A is rare. But, when crossing close relative individuals in the same kennel, it may happen, and an onset individual may be born incidentally. In the process of manifestation of an onset dog, crossing seen in Figure 1B would be repeated, there would be many carrier dogs in the kennel without being realized. For example, when a dog with a disease is found for the first time, immediately the dogs of the kennel may be examined, but there are already many carrier dogs int the kennel. This has happened in many cases.

GMI Gangliosidosis

A genetic disease often seen in Shiba dogs is gangliosidosis. GM1 gangliosidosis is one of 50 lysosome storage diseases. Due to the mutation of GLB1 gene (c1647delC), an enzyme β-galactosidase is absent to cause this lethal neurodegenerative disease. An onset dog would die at the age of a little over one with the clinical development (progressive movement, visual and cognition disorders) shown in Figure 2. Unfortunately, there is no effective treatment method for the disease. Gangliosidosis is manifested when a dog is still very young and cute, and the condition is gradually aggravated regardless of intensive care. At the final stage, the dog becomes unable to recognize the owner or caretaker and dies. The dog owner is exposed to tremendous mental stress (grief, illogicality, etc.) and the stress is converted into a great rage, which may lead to a trouble involving the breeder, seller and dog registration association.

Even if a breeder has never seen dogs contracted with gangliosidosis in his kennel in the past, it can’t be assured that there is no carrier dog of gangliosidosis in his kennel. The number of carriers may have increased without being noticed. Thus, when an onset dog is found, there should be quite a lot of carriers already and it is extremely difficult to take measures to prevent the disease at the time point.

Clinical course of GM1 gangliosidosis in Shiba dogs
Figure 2. Clinical course of GM1 gangliosidosis in Shiba dogs


Definite diagnosis of GM1 gangliosidosis was made in about 30 cases from Hokkaido to Kyushu in Japan. However, this doesn’t mean that the actual occurrences are 30 but that most of the onset cases just may have not been reported. Based on a randomly conducted survey on groups of Shiba dogs in whole Japan, the carrier rate is about 1 %. However, the carrier rate in Kinki region is about 3%, which is higher than other areas, and the rate is also expected to be higher in Chugoku and Shikoku regions. The carrier rate of 1 to 3% means one carrier in 30 to 100 Shiba dogs. Since 30,000 to 40,000 Shiba dogs are born annually, more than several hundreds of carriers are born annually. Furthermore, by crossing the carriers, several onset dogs are born per year. Regarding gangliosidosis, in the past 10 and more years (nearly 20 years), the author’s scientific literatures (for international journals) and commentaries (for veterinary magazines in Japan) have been widely published and the disease is well-known worldwide in the field of veterinary, but many veterinarians, breeders and owners in Japan are still unaware of the existence of this disease. Therefore, it is assumed that many onset dogs have not been diagnosed with gangliosidosis and died of unknown causes somewhere.

The first onset dog diagnosed by the author was a male dog born in 1997, however, it is assumed that the symptoms must have been manifested much earlier, and the dogs must have died with no clear causes found when they became a little over one year old in reality. It is also assumed that a mutation, which is the cause of this disease, happened even much earlier. It needs several or tens of years to see an onset dog since the occurrence of the mutation. In addition, excellent dogs which can be a champion in exhibitions may accidentally become a carrier. Because, as champion dogs are crossed with many female dogs, if a mutation happens in a champion dog, the mutation can be passed down to a lot of offspring. This is because when a carrier dog is crossed with a normal one, half of the baby dogs become carriers (refer to Figure 1). If a kennel accidentally has a campion dog which is also a carrier, dogs with the mutation to cause gangliosidosis must be prevailing in the kennel and the disease is spreading even outside of the kennel by crossing with dogs of other kennels. The phenomenon that a mutation rate suddenly increases in a certain population is called “founder phenomenon“. Starting from a kennel where a mutation is prevailing, onset dogs are sporadically reproduced unintentionally. Therefore, if you depend only on your experience that you have not seen an onset dog in your kennel, you may have a big problem.

Preventive measures

As the causal mutation for GM1 gangliosidosis in Shiba dogs was already clarified by the research of the author in 2002, genetic screening has been available since more than ten years ago. Although the author has claimed the importance of genetic screening on many and various occasions, the information has not been spread well in Japan and preventive measures have not been implemented, which is regrettable. On the other hand, people have been well-aware of the prevention of genetic diseases overseas, and we were requested by Shiba Dog Club overseas (Czech Republic) to conduct genetic screening of stud dogs there in around 2005 (Figure 3). The difference in the awareness between Japan and overseas is very clear.

The benefit of genetic screening is to enable diagnosis of not only onset dogs but also carrier dogs in a similar way. For the exam, only a small amount of DNA sample is needed, and the DNA sample can be extracted from a small amount of not only blood but also oral mucosa and saliva.

By excluding dogs judged to be a carrier from the reproduction line, gangliosidosis can be perfectly prevented. However, if a dog is extremely excellent but is also a carrier, the dog can be crossed with normal female dogs (Figure 1B), and all the offspring is screened to choose excellent baby dogs with normal genes for reproduction to pass down the excellent nature. When the number of carriers is rather high, if all the carriers are removed from the reproduction line, the inbreeding rate would increase and a risk that an unknown latent genetic disease might be manifested would increase as well. Therefore, a rapid increase in inbreeding rate should be avoided without failure. This is because too strict and quick measures to exterminate an existing genetic disease may cause an adverse effect to spread other multiple genetic diseases.

Shiba Dog Club in Czech Republic (in 2005) and DNA sampling (oral mucosa)
Figure 3. Shiba Dog Club in Czech Republic (in 2005) and DNA sampling (oral mucosa)

Carriers and animal ethics

Dogs judged to be a carrier by genetic screening are totally healthy and same as normal dogs as a pet. Although carriers should be avoided for the use of reproduction as much as possible (as described above, they may be crossed with normal dogs in some conditions in many cases), there is no problem to sell them as a pet (actually, they have been sold without screening). However, when carriers are sold or transferred as an inbreeding dog, it causes a very serious problem to degrade the trust in the whole association. Also, if there are some people who are against selling carrier dogs as a pet, they lack animal ethics and are unqualified for keeping a dog. Actually, it is considered that there are no animals including humans who are not any of genetic carriers, which means anybody has some genetic mutations. If carrier dogs are disposed of by humans, it is a big problem concerning animal ethics, and such kennels and organizations may not even be able to exist in the future. In the international society (Japan is part of the international society), breeders and organizations are required to act paying full attention to animal ethics.


I would repeat again that GM1 gangliosidosis in Shiba dogs is an internationally well-known fact now (from about 20 years ago). Highly conscious Shiba dog fans all over the world already know the content described here as common knowledge. Therefore, if a breeder, who is a specialist of Shiba dogs, or a veterinarian, who is a specialist of diseases, doesn’t know about this disease, he/she can’t give any excuse to the owner of a Shiba dog for the ignorance. Those breeders or veterinarians may lose people’s trust in them due to their lack of knowledge.

Everybody must feel that now is the age of accountability for not taking preventive measures. I wonder that the responsibility for not having taken preventive measures for a long time is under question now. We should take some measures now, otherwise we may have no future.


original article:

  1. Yamato O, Ochiai K, Masuoka Y, Hayashida E, Tajima M, Omae S, Iijima M, Umemura T, Maede Y. GM1 gangliosidosis in shiba dogs. Vet Rec 146, 493–496, 2000.
  2. 田中宏, 中山正成, 杉山優子, 大和修. 白血球リソソーム酵素測定により GM1 ガングリオシドーシス と診断された柴犬の 1 例. 日獣会誌 54, 625–627, 2001.
  3. Yamato O, Endoh D, Kobayashi A, Masuoka Y, Yonemura M, Hatakeyama A, Satoh H, Tajima M, Yamasaki M, Maede Y. A novel mutation in the gene of canine acid β-galactosidase that causes GM1-gangliosidosis in Shiba dogs. J Inherited Metab Dis 25, 525–526, 2002.
  4. Yamato O, Masuoka Y, Yonemura M, Hatakeyama A, Satoh H, Kobayashi A, Nakayama M, Asano T, Shoda T, Yamasaki M, Ochiai K, Umemura T, Maede Y. Clinical and clinico-pathologic characteristics of Shiba dogs with a deficiency of lysosomal acid β-galactosidase: A canine model of human GM1 gangliosidosis. J Vet Med Sci 65, 213–217, 2003.
  5. Satoh H, Yamato O, Asano T, Yamasaki M, Maede Y. Increased concentration of GM1-ganglioside in cerebrospinal fluid in dogs with GM1- and GM2-gangliosidoses and its clinical application for diagnosis. J Vet Diagn Invest 16, 223–226, 2004.
  6. Yamato O, Kobayashi A, Satoh H, Endoh D, Shoda T, Masuoka Y, Hatakeyama A, Jo EO, Asano T, Yonemura M, Yamasaki M, Maede Y. Comparison of polymerase chain reaction-restriction fragment length polymorphism assay and enzyme assay for diagnosis of GM1-gangliosidosis in Shiba dogs. J Vet Diagn Invest 16, 299–304, 2004.
  7. Yamato O, Jo EO, Shoda T, Yamasaki M, Maede Y. Rapid and simple mutation screening of GM1 gangliosidosis in Shiba dogs by direct amplification of deoxyribonucleic acid from various forms of canine whole-blood specimens. J Vet Diagn Invest 16, 469–472, 2004.
  8. Yamato O, Jo EO, Satoh H, Yamauchi T, Kobayashi A, Yamasaki M, Maede Y. Use of amnion and placenta in neonatal screening for canine GM1-gangliosidosis and the risk of diagnostic misclassifications. Vet Clin Pathol 35, 91–94, 2006.
  9. Satoh H, Yamato O, Asano T, Yonemura M, Yamauchi T, Hasegawa D, Orima H, Arai T, Yamasaki M, Maede Y. Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: Possible use for assessment of a therapeutic regimen. Brain Res 1133, 200–208, 2007.
  10. Yamato O, Jo EO, Chang HS, Satoh H, Shoda T, Sato R, Uechi M, Kawasaki N, Naito Y, Yamasaki M, Maede Y, Arai T. Molecular screening of canine GM1 gangliosidosis using blood smear specimens after prolonged storage: Detection of carriers among Shiba dogs in northern Japan. J Vet Diagn Invest 20, 68–71, 2008.
  11. Nagayasu A, Nakamura T, Yamato O, Tsuzuki K, Hosaka Y, Ueda H, Tangkawattana P, Takahana K. Morphological analysis of corneal opacity in Shiba dog in GM1 gangliosidosis. J Vet Med Sci 70, 881–886, 2008.
  12. 中本裕也, 大和修, 小澤剛, 長谷川大輔, 板本和仁, 方伯部健吾, 塚根美穂, 中市統三. 遺伝子検査に よりGM1ガングリオシドーシスと確定診断された柴犬3症例の頭部MRI所見. 日獣会誌62,219–224,2009.
  13. Yamato O, Funk H, Kawahara N, Funková M, Entlerová Z, Petrusová H, Hayashi D, Satoh H, Yamasaki M, Maede Y, Yabuki A, Arai T. Mutation screening of canine GM1 gangliosidosis for preventive measures: absence of the mutant allele in breeding shiba dogs in the Czech Republic. Jpn J Prophylactic Vet Med 1, 63–68, 2009.
  14. Chang HS, Arai T, Yabuki A, Hossain MA, Rahman MM, Mizukami K, Yamato O. Rapid and reliable genotyping technique for GM1 gangliosidosis in Shiba dogs by real-time polymerase chain reaction with TaqMan-minor groove binder probes. J Vet Diagn Invest 22, 234–237, 2010.
  15. Satoh H, Yamauchi T, Yamasaki M, Maede Y, Yabuki A, Chang HS, Asanuma T, Yamato O. Rapid detection of GM1 gangliosidosis in cerebrospinal fluid in dogs with GM1 gangliosidosis using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J Vet Diagn Invest 23, 1202–1207, 2011.
  16. Hasegawa D, Yamato O, Nakamoto Y, Ozawa T, Yabuki A, Itamoto K, Kuwabara T, Fujita M, Takahashi K, Mizoguchi S, Orima H. Serial MRI features of canine GM1 gangliosidosis: a possible imaging biomarker for diagnosis and progression of the disease. Sci World J 2012, 250197, 2012.
  17. Rahman MM, Kawaguchi H, Miyoshi N, Yabuki A, Nakamoto Y, Ozawa T, Yamato O. Pathological features of salivary gland cysts in a Shiba dog with GM1 gangliosidosis: a possible misdiagnosis as malignancy. J Vet Med Sci 74, 485–489 2012.
  18. Uddin MM, Arata S, Takeuchi Y, Chang HS, Mizukami K, Yabuki A, Rahman MM, Kohyama M, Hossain MA, Takayama K, Yamato O. Molecular epidemiology of canine GM1 gangliosidosis in the Shiba Inu breed in Japan: relationship between regional prevalence and carrier frequency. BMC Vet Res 9, 132, 2013.
  19. Hasegawa D, Tamura S, Nakamoto Y, Matsuki N, Takahashi K, Fujita M, Uchida K, Yamato O. Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases. PLoS One 8, e83455, 2013
  20. Kohyama M, Yabuki A, Ochiai K, Nakamoto Y, Uchida K, Hasegawa D, Takahashi K, Kawaguchi H, Tsuboi M, Yamato O. In situ detection of GM1 and GM2 gangliosides using immunohistochemical and immunofluorescent techniques for auxiliary diagnosis of canine and feline gangliosidoses. BMC Vet Res 12, 67, 2016.

review article:

  1. 大和修. 柴犬のGM1ガングリオシドーシス その発見から迅速遺伝子診断法の開発、そして予防・制圧へ. SAC No. 133, 13-22, 2003.
  2. 大和修. 特集先天性・遺伝性疾患, ライソゾーム蓄積病. SA Medicine 7(6), 49–63, 2005.
  3. 大和修. どうする!? 遺伝性疾患, 第6回 遺伝病の予防:その理想と現実 −柴犬のGM1ガングリオシドーシスに対する取り組みを例にあげて−. Clinic Note No. 27, 30–39, 2007.
  4. 大和修. 動物の先天代謝異常症:ライソゾーム病および関連疾患について. 鹿児島県獣医師会会報 第41号, 20(1), 2–7, 2008.
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  6. 中本裕也, 小澤剛, 矢吹映, 大和修. 柴犬のGM1ガングリオシドーシス 〜早期診断を導くために必要な知識〜. Clinic Note No. 58, 71–82, 2010.
  7. 大和修. 治療シリーズ〜私はこうしている〜神経・筋肉・関節疾患 ライソゾーム(蓄積)病. SA Medicine 12(6), 10–13, 2010.
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  10. 大和修. [特集] 臨床検査を極める. 遺伝子疾患の検査. JVM 獣医畜産新報. 68(10), 733–740, 2015. 11. 大和修. 症候シリーズ Vol. 11 運動失調・麻痺1 ライソゾーム蓄積病. SA Medicine 18(5), 6–9, 2016.


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