OMIA:001988-9615 : Copper toxicosis, COMMD1-related in Canis lupus familiaris (dog)

Categories: Liver/biliary system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 607238 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Renamed from 'Wilson disease, COMMD1 type' [10/01/2023]

Species-specific name: copper toxicosis, atypical form of Wilson disease

Species-specific symbol: CT

Species-specific description: Bedlington terrier copper toxicosis has been reported to be caused by a homozygous exon deletion in COMMD1 (Forman et al., 2005). However, copper toxicosis has since been diagnosed in Bedlington terriers lacking the COMMD1 deletion, and in these dogs the disease has been associated with two splice variants in the ABCA12 gene (Haywood et al. 2016) and a variant in the ATP7B gene that has been proposed as causal variant for Wilson disease (see OMIA:001071-9615 : Wilson disease in Canis lupus familiaris) (Haywood et al., 2023). Labrador retriever copper toxicosis is associated with a missense mutation in ATP7B (see OMIA:001071-9615 : Wilson disease in Canis lupus familiaris), and with a protective mutation in ATP7A (see OMIA:002608-9615 : Modifier of copper toxicosis, ATP7A-related in Canis lupus familiaris).

Mapping: Yuzbasiyan-Gurkan et al. (1997) performed a genome scan with 213 microsatellites on Bedlington Terrier families comprising 77 animals, 25 of which were affected. One closely linked (0 cM) microsatellite (C04107) was identified. van der Sluis et al. (1999) FISH-mapped a BAC clone containing this microsatellite to a metaphase spread of canine chromosomes, showing that the marker, and hence the disorder gene, is on canine chromosome CFA10q26, in a region of conserved synteny with human chromosome HSA2p13–p16. Detailed analysis of this BAC revealed sequence highly similar to that of an exon of the MURR1 gene of humans and mouse. Radiation-hybrid mapping of this gene revealed it to be located in HSA2p13–p16, i.e. the region showing conserved synteny with the region of CFA10 that includes the canine disorder gene. Haywood et al. (2016) reported that the causal gene for non-COMMD1 Bedligton Terriers with this disorder maps to chromosome 30 in a region that "contains the ABCA12 gene which bears a close functional relationship to ATP-ase 7B responsible for Wilson's disease in man."

Markers: Even though the chromosomal location of microsatellite C04107 was not then known, it proved to be a very useful marker for identifying carriers (Holmes et al., 1998).

Molecular basis: van der Sluis et al. (2002) refined "the localization of the copper toxicosis gene to a region of <500 kb [in CFA10q26] by linkage disequilibrium mapping. While screening genes and expressed sequence tags in this region for mutations we found that exon 2 of the MURR1 gene is deleted in both alleles of all affected Bedlington terriers and in single alleles in obligate carriers." Detailed study of this deletion enabled Forman et al. (2005) to report that the deletion "breakpoints were positioned at 65.3091 and 65.3489 Mb of dog chromosome 10, in intron 1 and intron 2 of COMMD1 respectively, a deletion of 39.7 kb. The two breakpoints share sequence homology suggesting that homologous recombination may have been responsible for the deletion". Wu et al. (2020) concluded that "COMMD1 did not play a major role in the aetiology of copper associated hepatitis in Labrador retrievers and Dobermans" Haywood et al. (2023) “Liver and DNA samples from 24 COMMD1 affected and 10 unaffected Bedlingtons were assessed for copper and genetic variants.” The authors tested for variants in COMMD1 (OMIA variant ID:643), ATP7B (OMIA variant ID:106), ATP7A (OMIA variant ID:107) and 2 SNPs in ABCA12 (Haywood et al., 2016). “All affected dogs were homozygous for either the COMMD1 deletion or the ATP7B variant. … Two of the 10 normal dogs were wild type for all genes investigated, none was homozygous for the COMMD1 deletion and only three were homozygous for the ATP7B variant. … All dogs only carried the ATP7A:c.980C allele and were therefore negative for the protective mutation. … The two ABCA12 SNPs were seen to be widespread in Bedlington terriers and there was no obvious difference between affected and control dogs. … The results suggest that ATP7B mutations may play an important role in CT in COMMD1+/+ Bedlington terriers because of the high frequency of the mutated allele in affected dogs compared with control normal Bedlington terrier dogs, including homozygous ATP7B:c.4358A in all but one affected COMMD1+/+ dog. … The role of the ABCA12 SNPs remains unclear. It is likely that CT in Bedlington terriers and other breeds is a polygenic disease involving an interaction between a number of genes involved in copper transport and dietary copper intake.”

Clinical features: Su et al. (1982): Bedlington terriers with copper toxicosis initially present clinically normal despite increases in hepatic and renal and later brain copper levels. "The dogs's ceruloplasmin level is reported to be normal, Kayser-Fleischer rings have not been observed, and neurological manifestations are lacking. However, owners of these dogs have noted significant personality changes preceding symptoms of the hepatic disease" which occurs as disease is progressing. Favier et al. (2012) report longitudinal follow up of 5 COMMD-1 deficient Bedlington terriers until the age of 42 month: "During the entire follow-up period dogs showed no abnormalities at physical examination. Serum ALT was significantly increased at 24, 36, and 42 months of age (2–3-fold), whereas serum AP significantly increased at 18 and 42 months of age. During the 42 months follow-up period, bile acids and albumin remained within reference limits ... ." Acute clinical signs of hepatic disease in older animals include depression, vomiting, anorexia, prolonged capillary refill time, weight loss and jaundice. Chronic courses involve less severe signs but can include ascites, polydipsic and behavioural changes due to hepatic encephalopathy (Washabau, 2013; Herrtage et al., 1987). IT thanks DVM student Xinlin Dong, who provided the basis of this contribution in May 2023.

Pathology: An elevated hepatic copper concentration (normal mean is 206 ± 56 μg/g dry weight of liver in Bedlington terriers) with age is the key pathological feature found by liver biopsy and quantitative analysis. In the early stage, the hepatic copper concentration is between 400 and 1500 μg/g, and copper mainly accumulates in zone 3 with unremarkable histopathological founds. When the hepatic copper concentration is between 1500 and 2000 μg/g, accumulated copper is also found in zone 2 and zone 1 with focal hepatitis on biopsy. Chronic hepatitis or cirrhosis appears on biopsy when the hepatic copper concentration exceeds 2000 μg/g (Washabau, 2013). The longitudinal study by Favier et al. (2023) reports that at "six months of age all dogs showed a moderate centrilobular hepatic copper accumulation; however no evidence of copper laden Kupffer cells ... or other evidence of hepatitis was observed at this stage ... . At 12 months of age all animals had extensive copper accumulation diffuse throughout the lobules and in two animals a mild hepatitis was present. At 18 months all dogs showed a slight to mild hepatitis. Although there was some individual variation, the activity of hepatitis progressed to mild and moderate at older age (>24 months) in all dogs." IT thanks DVM student Xinlin Dong, who provided the basis of this contribution in May 2023.

Prevalence: Haywood et al. (2023) "The prevalence [of copper toxicosis] in this breed was very high in the 1970s and 1980s, ranging from 26% to 46% in different Bedlington terrier populations (Kelly et al., 1984). ... The COMMD1 deletion is no longer the predominant cause of CT in Bedlington terriers. Testing for the deletion is still indicated prior to breeding, because it remains present in the breed, but copper storage disease cannot be ruled out by demonstrating that a dog is COMMD1+/+. Liver biopsies are necessary to rule this out."

Genetic testing: One of the many laboratories offering a DNA test for this disorder is Dr. Van Haeringen Laboratorium B.V: www.vhlgenetics.com

Breed: Bedlington Terrier (Dog) (VBO_0200137).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COMMD1 copper metabolism (Murr1) domain containing 1 Canis lupus familiaris 10 NC_051814.1 (62894268..63067243) COMMD1 Homologene, Ensembl , NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
643 Bedlington Terrier (Dog) Wilson disease, COMMD1 type COMMD1 deletion, gross (>20) Naturally occurring variant 10 deletion "breakpoints were positioned at 65.3091 and 65.3489 Mb of dog chromosome 10, in intron 1 and intron 2 of COMMD1 respectively, a deletion of 39.7 kb" 2005 16293123

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:001988-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Mutton, J., Yeomans, S., White, J. :
Copper hepatopathies in Australian dogs. Aust Vet J , 2024. Pubmed reference: 38682427. DOI: 10.1111/avj.13338.
2023 Haywood, S., Swinburne, J., Schofield, E., Constantino-Casas, F., Watson, P. :
Copper toxicosis in Bedlington terriers is associated with multiple independent genetic variants. Vet Rec :e2832, 2023. Pubmed reference: 37038639. DOI: 10.1002/vetr.2832.
Kennedy, L., Ollier, B. :
Untangling the genetic traits underlying the development of copper toxicosis in Bedlington terriers. Vet Rec 193:154-156, 2023. Pubmed reference: 37594835. DOI: 10.1002/vetr.3386.
Wooton-Kee, C.R. :
Therapeutic implications of impaired nuclear receptor function and dysregulated metabolism in Wilson's disease. Pharmacol Ther :108529, 2023. Pubmed reference: 37741465. DOI: 10.1016/j.pharmthera.2023.108529.
2021 Corbee, R.J., Penning, L.C. :
COMMD1 exemplifies the power of inbred dogs to dissect genetic causes of rare copper-related disorders. Animals (Basel) 11:601, 2021. Pubmed reference: 33668783. DOI: 10.3390/ani11030601.
2020 Kruitwagen, H.S., Oosterhoff, L.A., van Wolferen, M.E., Chen, C., Nantasanti Assawarachan, S., Schneeberger, K., Kummeling, A., van Straten, G., Akkerdaas, I.C., Vinke, C.R., van Steenbeek, F.G., van Bruggen, L.W.L., Wolfswinkel, J., Grinwis, G.C.M., Fuchs, S.A., Gehart, H., Geijsen, N., Vries, R.G., Clevers, H., Rothuizen, J., Schotanus, B.A., Penning, L.C., Spee, B. :
Long-term survival of transplanted autologous canine liver organoids in a COMMD1-deficient dog model of metabolic liver disease. Cells 9:410, 2020. Pubmed reference: 32053895. DOI: 10.3390/cells9020410.
Wu, X., Mandigers, P.J.J., Fieten, H., Leegwater, P.A. :
Evaluation of COMMD1 in copper toxicosis in Labrador retrievers and Dobermans. Vet J 265:105561, 2020. Pubmed reference: 33129558. DOI: 10.1016/j.tvjl.2020.105561.
2019 Kruitwagen, H.S., Penning, L.C. :
Preclinical models of Wilson's disease, why dogs are catchy alternatives. Ann Transl Med 7:S71, 2019. Pubmed reference: 31179308. DOI: 10.21037/atm.2019.02.06.
Kruitwagen, H.S., Fieten, H., Penning, L.C. :
Towards bioengineered liver stem cell transplantation studies in a preclinical dog model for inherited copper toxicosis. Bioengineering (Basel) 6:88, 2019. Pubmed reference: 31557851. DOI: 10.3390/bioengineering6040088.
Wang, X., Garrick, M.D., Collins, J.F. :
Animal models of normal and disturbed iron and copper metabolism. J Nutr 149:2085-2100, 2019. Pubmed reference: 31504675. DOI: 10.1093/jn/nxz172.
2014 Fieten, H., Penning, L.C., Leegwater, P.A., Rothuizen, J. :
New canine models of copper toxicosis: diagnosis, treatment, and genetics. Ann N Y Acad Sci 1314:42-8, 2014. Pubmed reference: 24758744. DOI: 10.1111/nyas.12442.
2013 Washabau, R.J. :
Chapter 61 – Liver. Canine and Feline Gastroenterology, R.J. Washabau & M.J. Day (Ed.), W.B. Saunders. :890-891, 2013.
2012 Favier, R.P., Spee, B., Schotanus, B.A., van den Ingh, T.S., Fieten, H., Brinkhof, B., Viebahn, C.S., Penning, L.C., Rothuizen, J. :
COMMD1-deficient dogs accumulate copper in hepatocytes and provide a good model for chronic hepatitis and fibrosis. PLoS One 7:e42158, 2012. Pubmed reference: 22879914. DOI: 10.1371/journal.pone.0042158.
2011 Favier, R.P., Spee, B., Penning, L.C., Rothuizen, J. :
Copper-induced hepatitis: the COMMD1 deficient dog as a translational animal model for human chronic hepatitis. Vet Q 31:49-60, 2011. Pubmed reference: 22029820. DOI: 10.1080/01652176.2011.563146.
2008 Coronado, V.A., O'Neill, B., Nanji, M., Cox, D.W. :
Polymorphisms in canine ATP7B: candidate modifier of copper toxicosis in the Bedlington terrier. Vet J 177:293-6, 2008. Pubmed reference: 17572118. DOI: 10.1016/j.tvjl.2007.04.012.
2007 Lee, S.A., Fillipich, L.J., Hyun, C. :
Prevalence of the exon 2 deletion of the COMMD1 gene in Australian Bedlington terriers. J Genet 86:289-91, 2007. Pubmed reference: 18305350.
Spee, B., Arends, B., van Wees, A.M., Bode, P., Penning, L.C., Rothuizen, J. :
Functional consequences of RNA interference targeting COMMD1 in a canine hepatic cell line in relation to copper toxicosis. Anim Genet 38:168-70, 2007. Pubmed reference: 17355395. DOI: 10.1111/j.1365-2052.2007.01580.x.
2006 Haywood, S. :
Copper toxicosis in Bedlington terriers. Vet Rec 159:687, 2006. Pubmed reference: 17099181.
Lovicu, M., Dessì, V., Lepori, M.B., Zappu, A., Zancan, L., Giacchino, R., Marazzi, M.G., Iorio, R., Vegnente, A., Vajro, P., Maggiore, G., Marcellini, M., Barbera, C., Kostic, V., Farci, A.M., Solinas, A., Altuntas, B., Yuce, A., Kocak, N., Tsezou, A., De Virgiliis, S., Cao, A., Loudianos, G. :
The canine copper toxicosis gene MURR1 is not implicated in the pathogenesis of Wilson disease. J Gastroenterol 41:582-7, 2006. Pubmed reference: 16868807. DOI: 10.1007/s00535-006-1807-0.
Wu, Z.Y., Zhao, G.X., Chen, W.J., Wang, N., Wan, B., Lin, M.T., Murong, S.X., Yu, L. :
Mutation analysis of 218 Chinese patients with Wilson disease revealed no correlation between the canine copper toxicosis gene MURR1 and Wilson disease. J Mol Med (Berl) 84:438-42, 2006. Pubmed reference: 16649058. DOI: 10.1007/s00109-005-0036-y.
2005 Forman, OP., Boursnell, ME., Dunmore, BJ., Stendall, N., van den Sluis, B., Fretwell, N., Jones, C., Wijmenga, C., Rothuizen, J., van Oost, BA., Holmes, NG., Binns, MM., Jones, P. :
Characterization of the COMMD1 (MURR1) mutation causing copper toxicosis in Bedlington terriers. Anim Genet 36:497-501, 2005. Pubmed reference: 16293123. DOI: 10.1111/j.1365-2052.2005.01360.x.
2004 Hyun, C., Lavulo, LT., Filippich, LJ. :
Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia. Am J Vet Res 65:1573-9, 2004. Pubmed reference: 15566097.
Hyun, C., Filippich, LJ. :
Inherited canine copper toxicosis in Australian Bedlington Terriers. J Vet Sci 5:19-28, 2004. Pubmed reference: 15028882.
Stuehler, B., Reichert, J., Stremmel, W., Schaefer, M. :
Analysis of the human homologue of the canine copper toxicosis gene MURR1 in Wilson disease patients. J Mol Med 82:629-34, 2004. Pubmed reference: 15205742. DOI: 10.1007/s00109-004-0557-9.
2003 Coronado, VA., Damaraju, D., Kohijoki, R., Cox, DW. :
New haplotypes in the Bedlington terrier indicate complexity in copper toxicosis. Mamm Genome 14:483-91, 2003. Pubmed reference: 12925897. DOI: 10.1007/s00335-002-2255-3.
Klomp, AE., van de Sluis, B., Klomp, LW., Wijmenga, C. :
The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis. J Hepatol 39:703-9, 2003. Pubmed reference: 14568250.
Muller, T., van de Sluis, B., Zhernakova, A., van Binsbergen, E., Janecke, A.R., Bavdekar, A., Pandit, A., Weirich-Schwaiger, H., Witt, H., Ellemunter, H., Deutsch, J., Denk, H., Muller, W., Sternlieb, I., Tanner, M.S., Wijmenga, C. :
The canine copper toxicosis gene MURR1 does not cause non-Wilsonian hepatic copper toxicosis Journal of Hepatology 38:164-8, 2003. Pubmed reference: 12547404.
Proschowsky, HF., Olsen, JB., Jepsen, B., Fredholm, M. :
Evaluation of the present breeding programme against copper toxicosis in Danish Bedlington terriers. Anim Genet 34:142-5, 2003. Pubmed reference: 12648098.
van de Sluis, B., Peter, AT., Wijmenga, C. :
Indirect molecular diagnosis of copper toxicosis in Bedlington terriers is complicated by haplotype diversity. J Hered 94:256-9, 2003. Pubmed reference: 12816967.
2002 Hyun, C., Filippich, L.J. :
Inherited copper toxicosis in a Bedlington Terrier - a case report Australian Veterinary Practitioner 32:152-159, 2002.
Kawamura, M., Takahashi, I., Kaneko, J.J. :
Ultrastructural and kinetic studies of copper metabolism in Bedlington Terrier dogs Veterinary Pathology 39:747-750, 2002. Pubmed reference: 12450209.
van de Sluis, B., Rothuizen, J., Pearson, P.L., van Oost, B.A., Wijmenga, C. :
Identification of a new copper metabolism gene by positional cloning in a purebred dog population Human Molecular Genetics 11:165-173, 2002. Pubmed reference: 11809725.
2001 Seguin, M.A., Bunch, S.E. :
Iatrogenic copper deficiency associated with long-term copper chelation for treatment of copper storage disease in a Bedlington Terrier Journal of the American Veterinary Medical Association 218:1593-+, 2001. Pubmed reference: 11393371.
2000 Haywood, S., Fuentealba, I.C., Kemp, S.J. :
Copper toxicosis in Bedlington terriers Veterinary Record 146:383-384, 2000. Pubmed reference: 10803990.
Holmes, N.G., Binns, M.M., Herrtage, M.E. :
DNA testing for copper toxicosis in Bedlington terriers Veterinary Record 146:739, 2000. Pubmed reference: 10901220.
Proschowsky, H.F., Jepsen, B., Jensen, H.E., Jensen, A.L., Fredholm, M. :
Microsatellite marker C04107 as a diagnostic marker for copper toxicosis in the Danish population of Bedlington terriers Acta Veterinaria Scandinavica 41:345-350, 2000. Pubmed reference: 11234968.
Ubbink, G.J., Van, den, Ingh, T.S.G.A.M., Yuzbasiyan-Gurkan, V., Teske, E., Van, de, Broek, J., Rothuizen, J. :
Population dynamics of inherited copper toxicosis in Dutch Bedlington terriers (1977-1997) Journal of Veterinary Internal Medicine 14:172-176, 2000. Pubmed reference: 10772489.
van de Sluis, B., Kole, S., van Wolferen, M., Holmes, N.G., Pearson, P.L., Rothuizen, J., van, Oost, B.A., Wijmenga, C. :
Refined genetic and comparative physical mapping of the canine copper toxicosis locus Mammalian Genome 11:455-460, 2000. Pubmed reference: 10818210.
1999 Dagenais, S.L., Guevara-Fujita, M., Loechel, R., Burgess, A.C., Miller, D.E., Yuzbasiyan-Gurkan, V., Brewer, G.J., Glover, T.W. :
The canine copper toxicosis locus is not syntenic with ATP7B or ATX1 and maps to a region showing homology to human 2p21 Mammalian Genome 10:753-756, 1999. Pubmed reference: 10384054.
Nanji, M.S., Cox, D.W. :
The copper chaperone Atox1 in canine copper toxicosis in Bedlington terriers Genomics 62:108-112, 1999. Pubmed reference: 10585777. DOI: 10.1006/geno.1999.5983.
Rothuizen, J., Ubbink, G.J., van, Zon, P., Teske, E., van, den, Ingh, T.S.G.A.M., Yuzbasiyan-Gurkan, V. :
Diagnostic value of a microsatellite DNA marker for copper toxicosis in West-European Bedlington terriers and incidence of the disease Animal Genetics 30:190-194, 1999. Pubmed reference: 10442980.
van de Sluis, B.J.A., Breen, M., Nanji, M., van Wolferen, M., de Jong, P., Binns, M.M., Pearson, P.L., Kuipers, J., Rothuizen, J., Cox, D.W., Wijmenga, C., van Oost, B.A. :
Genetic mapping of the copper toxicosis locus in Bedlington terriers to dog chromosome 10, in a region syntenic to human chromosome region 2p13-p16 Human Molecular Genetics 8:501-507, 1999. Pubmed reference: 9949209.
1998 Holmes, N.G., Herrtage, M.E., Ryder, E.J., Binns, M.M. :
DNA marker C04107 for copper toxicosis in a population of Bedlington Terriers in the United Kingdom Veterinary Record 142:351-352, 1998. Pubmed reference: 9587195.
1997 Yuzbasiyan-Gurkan, V., Blanton, S.H., Cao, Y.Y., Ferguson, P., Li, J.P., Venta, P.J., Brewer, G.J. :
Linkage of a microsatellite marker to the canine copper toxicosis locus in Bedlington terriers American Journal of Veterinary Research 58:23-27, 1997. Pubmed reference: 8989491.
1996 Rothuizen, J., Vanwolferen, M., Yuzbasiangurkan, V. :
Evaluation of a DNA marker for copper toxicosis in Bedlington Terriers Veterinary Quarterly 18:S 54, 1996.
1993 Yuzbasiyangurkan, V., Wagnitz, S., Blanton, S.H., Brewer, G.J. :
Linkage studies of the esterase-D and retinoblastoma genes to canine copper toxicosis - A model for Wilson disease. Genomics 15:86-90, 1993. Pubmed reference: 8432554. DOI: 10.1006/geno.1993.1013.
1992 Teske, E., Brinkhuis, B.G.A.M., Bode, P., Vandeningh, T.S.G.A.M., Rothuizen, J. :
Cytological detection of copper for the diagnosis of inherited copper toxicosis in Bedlington terriers. Veterinary Record 131:30-32, 1992. Pubmed reference: 1380748.
1991 Kolb, E., Nestler, K., Piechotta, D. :
Studies of copper metabolism in dogs - The development, treatment and prevention of copper storage disease in Bedlington and other terriers. Tierarztliche Umschau 46:93-97, 1991.
1988 Twedt, D.C., Hunsaker, H.A., Allen, K.G. :
Use of 2,3,2-tetramine as a hepatic copper chelating agent for treatment of copper hepatotoxicosis in Bedlington terriers. J Am Vet Med Assoc 192:52-6, 1988. Pubmed reference: 3343179.
1987 Herrtage, M.E., Seymour, C.A., White, R.A.S., Small, G.M., Wight, D.G.D. :
Inherited copper toxicosis in the Bedlington terrier: the prevelance in asymptomatic dogs Journal of Small Animal Practice 28:1141-1151, 1987.
Herrtage, M.E., Seymour, C.A., White, R.A.S., Small, G.M., Wight, D.G.D. :
Inherited copper toxicosis in the Bedlington terrier: a report of two clinical cases Journal of Small Animal Practice 28:1127-1140, 1987.
1984 Johnson, G.F., Gilbertson, S.R., Goldfisher, S., Grushoff, P.S., Sternlieb, I. :
Cytochemical detection of copper toxicosis of Bedlington terriers Veterinary Pathology 21:57-60, 1984. Pubmed reference: 6710813.
1983 Eriksson, J. :
Copper toxicosis in Bedlington terriers Acta Veterinaaria Scandinavica 24:148-152, 1983.
Owen, C.A., McCall, J.T. :
Identification of the carrier of the Bedlington Terrier copper disease. Am J Vet Res 44:694-6, 1983. Pubmed reference: 6869968.
Robertson, H.M., Studdert, V.P., Reuter, R.E. :
Inherited copper toxicosis in Bedlington terriers Australian Veterinary Journal 60:235-238, 1983. Pubmed reference: 6639527.
1982 Owen, C.A., Ludwig, J. :
Inherited copper toxicosis in Bedlington terriers American Journal of Pathology 106:432-434, 1982. Pubmed reference: 7065120.
Su, L.C., Ravenshad, S., Owen, C.A., McCall, J.T., Zollman, P.E., Hardy, R.M. :
A comparison of copper-loading disease in Bedlington Terriers and Wilson's disease in humans American Journal of Physiology 243:G226-G230, 1982. Pubmed reference: 7114265.
1981 Sternlieb, I. :
Copper toxicosis of the Bedlington terrier. J Rheumatol Suppl 7:94-5, 1981. Pubmed reference: 6939891.
1980 Johnson, G.F., Sternlieb, I., Twedt, D.C., Grushoff, P.S., Scheinberg, I.H. :
Inheritance of copper toxicosis in Bedlington Terriers American Journal of Veterinary Research 41:1865-1866, 1980. Pubmed reference: 7212417.
1977 Hardy, R.M. :
Chronic hepatitis in Bedlington Terriers - An emerging animal model D.V.M. 8:20 only, 1977.
1975 Hardy, R.M., Stevens, J.B., Stowe, C.M. :
Chronic progressive hepatitis in Bedlington Terriers associated with elevated liver copper concentrations Minnesota Veterinarian 15:13-24, 1975.

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