Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia

Hyun, Changbaig; Lavulo, Lopeti; Filippich, L. J.

doi:10.2460/ajvr.2004.65.1573

Cited by 17 publications

(13 citation statements)

References 19 publications

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“…Recently, however, some ct -affected Bedlington terriers have been identified without the homozygous commd1 deletion in both the uk , usa and Australia (Coronado and others 2003, Hyun and others 2004), reinforcing earlier voiced concerns. Since no other commd1 mutation could be found in them, we (Haywood and van de Sluis) have hypothesised that a second as yet unknown disease gene is involved in Bedlington ct and have received funding from the Kennel Club to try to identify this gene.…”

mentioning

confidence: 87%

Copper toxicosis in Bedlington terriers

Haywood¹

2006

Veterinary Record

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confidence: 87%

Copper toxicosis in Bedlington terriers

Haywood¹

2006

Veterinary Record

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“…Deficiency of Murr1 is the main cause for copper toxicosis in dogs, 1,26,69,70 and co-precipitation experiments suggest a direct interaction with the WDP. 30 -32 In our hands, there was no co-localization between Murr1/ COMMD1 on membrane vesicular structures and ATP7B (Figure 4, A-C).…”

Section: Discussionmentioning

confidence: 99%

Copper-Induced Translocation of the Wilson Disease Protein ATP7B Independent of Murr1/COMMD1 and Rab7

Weiss

Carbajo-Lozoya

Tuma

et al. 2008

The American Journal of Pathology

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Wilson disease is a genetic disorder of copper metabolism. Impaired biliary excretion results in a gradual accumulation of copper, which leads to severe disease. The specific gene defect lies in the Wilson disease protein, ATP7B, a copper-transporting ATPase that is highly active in hepatocytes. The two major functions of ATP7B in the liver are the copper loading of ceruloplasmin in the Golgi apparatus, and the excretion of excess copper into the bile. In response to elevated copper levels, ATP7B shows a unique intracellular trafficking pattern that is required for copper excretion from the Golgi apparatus into dispersed vesicles. We analyzed the translocation of ATP7B by both confocal microscopy and RNA interference, testing current models that suggest the involvement of Murr1/COMMD1 and Rab7 in this pathway. We found that although the ATP7B translocation is conserved among nonhepatic cell lines, there is no co-localization with Murr1/COMMD1 or the Rab marker proteins of the endolysosomal system. Consistent with this finding, the translocation of ATP7B was not impaired by the depletion of either Murr1/COMMD1 or Rab7, or by a dominant-negative Rab7 mutant. In conclusion, our data suggest that the translocation of ATP7B takes place independently of Rab7-regulated endosomal traffic events. Murr1/COMMD1 plays a role in a later step of the copper excretion pathway but is not involved in the translocation of the Wilson disease protein.

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“…Positional cloning efforts determined that an~10 kb deletion involving exon 2 of the COMMD1 gene is associated with the disease phenotype in European pedigrees [5] , and subsequent studies in Australia have observed that all dogs homozygous for this deletion develop the disorder [40] . Consistent with a disease-causing role for this COMMD1 mutation, the protein is absent in affected animals that are homozygous for the exon 2 deletion [8] .…”

Section: Commd1 As a Regulator Of Copper Metabolismmentioning

confidence: 99%

“…Moreover, reduction of COMMD1 expression by RNA interference results in increased accumulation of copper in human embryonic kidney cells [7] and in dog hepatic cells [41] , supporting the notion that COMMD1 plays a role in the control of intracellular copper levels. More recently, it has been demonstrated that not all affected Bedlington terriers carry a deletion in exon 2 of the COMMD1 gene; some affected animals are heterozygous for the COMMD1-deleted state or even carry two alleles without this deletion [40,42]. To date, no disease-causing mutations have been found in the COMMD1 coding sequence or splice sites of nondeleted alleles that segregate with the disorder, raising questions about the nature of the mutation that results in copper toxicosis in these animals.…”

Section: Commd1 As a Regulator Of Copper Metabolismmentioning

confidence: 99%

COMMD proteins: COMMing to the scene

Maine

Burstein

2007

Cell. Mol. Life Sci.

100

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COMM Domain-containing or COMMD proteins are a recently discovered group of factors defined by the presence of a unique motif in their extreme carboxy termini (Copper metabolism MURR1, or COMM domain). This protein family is comprised of ten members which are widely conserved throughout evolution and share certain functional properties. At the present time, a number of seemingly discrete functions have been ascribed to these factors. These include the regulation of such events as the activity of the transcription factor NF-kappaB, copper homeostasis, the function of the epithelial sodium channel, and cell proliferation. A unifying mechanism that would explain all these events is lacking at the moment, but recent studies suggest that regulation of the ubiquitin pathway may be the basis of many of the functions of the COMMD protein family.

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Evaluation of haplotypes associated with copper toxicosis in Bedlington Terriers in Australia

Cited by 17 publications

References 19 publications

Copper toxicosis in Bedlington terriers

Copper toxicosis in Bedlington terriers

Copper-Induced Translocation of the Wilson Disease Protein ATP7B Independent of Murr1/COMMD1 and Rab7

COMMD proteins: COMMing to the scene

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