scholarly journals Copper metabolism in mottled mouse mutants: copper therapy of brindled (Mobr) mice

1979 ◽  
Vol 180 (3) ◽  
pp. 605-612 ◽  
Author(s):  
J R Mann ◽  
J Camakaris ◽  
D M Danks ◽  
E G Walliczek
Keyword(s):  
Growth Response ◽  
Copper Deficiency ◽  
Lysyl Oxidase ◽  
Sebacic Acid ◽  
Copper Metabolism ◽  
Single Subcutaneous Injection ◽  
Mouse Mutants ◽  
Brindled Mouse ◽  
Copper Therapy ◽  
Early Effects

Copper therapy was applied to brindled mouse mutants, which suffer from lethal hypocupraemia, by using cuprous and cupric solutions. The method of treatment was a single subcutaneous injection of 50 microgram of copper at 7 days of age. Early effects of the dose were: prevention of the tremors and spasms seen in untreated mutants, raising to normal and near-normal of caeruloplasmin oxidase and lysyl oxidase activities and pigmentation of skin and fur. Growth of mutants was retarded up to 23 days of age, but thereafter they rapidly gained weight to be nearly normal by 60 days of age. At 3 days after injection, copper concentrations in previously deficient mutant organs apart from liver were at least as much as those of treated normals, which had remained unchanged. Copper in mutant livers had increased only slightly in comparison with the normal control. A state of copper deficiency recurred in mutant tissues by 25 days after injection. A solution of Cu+, retained as such by an alkyl polyether, and sebacic acid resulted in greater growth rates after 23 days than did three other copper treatments. Cu+ may have resulted in an improved growth response owing to it being more readily metabolized than C12+. Delayed release of copper from the site of injection may have played an important role.

scholarly journals Copper metabolism in mottled mouse mutants. The effect of copper therapy on lysyl oxidase activity in brindled (Mobr) mice

1982 ◽  
Vol 202 (2) ◽  
pp. 369-371 ◽  
Author(s):  
P M Royce ◽  
J Camakaris ◽  
J R Mann ◽  
D M Danks
Keyword(s):  
Acid Solution ◽  
Subcutaneous Injection ◽  
Oxidase Activity ◽  
Lysyl Oxidase ◽  
Sebacic Acid ◽  
Copper Metabolism ◽  
Single Subcutaneous Injection ◽  
Mouse Mutants ◽  
Copper Therapy ◽  
Effect Of Copper

Lysyl oxidase activity in extracts of skin from 1-day-old Mobr/Y mice was found to be between 50 and 60% of that in corresponding extracts from littermate +/Y mice of the same age. It was increased to 84-150% of that in the latter by prior treatment of the Mobr/Y mice at 7 days of age with a single subcutaneous injection of 50 micrograms of copper, retained as Cu+ in an alkyl polyether/sebacic acid solution. This suggests that in this form the copper is able to by-pass the block in copper metabolism and is deliverable to copper-requiring processes.

Studies on copper and cobalt therapy of cattle in central coastal Queensland

1967 ◽  
Vol 18 (1) ◽  
pp. 169 ◽  
Author(s):  
GI Alexander ◽  
JM Harvey ◽  
JH Lee ◽  
WC Stubbs
Keyword(s):  
Growth Response ◽  
Copper Deficiency ◽  
Copper Metabolism ◽  
Subcutaneous Injections ◽  
Liver Copper ◽  
Copper Status ◽  
Period 2 ◽  
Copper Supplementation ◽  
Copper Therapy ◽  
Effect Of Copper

Four experiments described determined the effect of copper and cobalt therapy on the growth and productivity of cattle on the marine plains of central coastal Queensland. Copper was administered by subcutaneous injections of copper glycinate, and cobalt by dosing per os with heavy cobalt pellets. The growth of weaned cattle was significantly improved by copper, particularly from June to October when limited palatable feed on the high ground forced the animals to forage on the para grass swamps. During the same period, 2-year-old heifers also showed a growth response to copper. Their conception rate increased after 19 months of copper therapy but not after 10.5 months. The growth rate of their calves bas significantly increased by copper supplementation. Liver copper concentrations were always low in untreated cattle. Copper therapy maintained these reserves at higher levels, which varied according to the season and the rate of growth of the animals. Calves born to treated cows had higher initial liver copper reserves than those from untreated cows, but in the absence of copper therapy these reserves declined to low and comparable levels in all calves at weaning. Pasture analyses suggest that the copper deficiency revealed was due to interference with copper metabolism rather than to a low copper status in the diet; this interference did not appear to be due to molybdenum. Weaned cattle appeared to respond to cobalt during 1960 but not subsequently, while the cows and calves showed no response. The vitamin B12 status in liver and serum appeared adequate in both treated and untreated cattle.

COPPER DEFICIENCY COMPLICATING SEVERE CHRONIC INTESTINAL MALABSORPTION

PEDIATRICS ◽  
1966 ◽  
Vol 38 (4) ◽  
pp. 596-604
Author(s):  
Angel Cordano ◽  
George G. Graham
Keyword(s):  
Enzyme Activity ◽  
Growth Response ◽  
Copper Deficiency ◽  
Dramatic Improvement ◽  
Lactase Deficiency ◽  
Intestinal Malabsorption ◽  
Pathological Fractures ◽  
Severe Diarrhea ◽  
Copper Therapy ◽  
Intestinal Enzyme

A case of chronic, severe diarrhea and maldigestion beginning in early infancy and possibly due to primary lactase deficiency is presented. By the age of 19 months, this had resulted in marked copper deficiency with anemia, neutropenia, osteoporosis, pathological fractures and probably aggravation of intestinal enzyme activity deficiency. At 6 4/12 years of age copper therapy produced a dramatic improvement in all manifestations, including the maldigestion, and there was a striking growth response.

scholarly journals Copper metabolism in mottled mouse mutants: distribution of 64Cu in brindled (Mobr) mice

1979 ◽  
Vol 180 (3) ◽  
pp. 613-619 ◽  
Author(s):  
J R Mann ◽  
J Camakaris ◽  
D M Danks
Keyword(s):  
Small Intestine ◽  
Copper Deficiency ◽  
Copper Metabolism ◽  
Mutant Mice ◽  
Distal Small Intestine ◽  
Suckling Mice ◽  
Mouse Mutants ◽  
Intracardiac Injection ◽  
Initial Uptake ◽  
Excessive Accumulation

1. Duodenal injection of 64Cu in treated adult mutant mice (Mobr/y) revealed severe malabsorption of copper. In suckling mutants, malabsorption was less severe, owing to delayed absorption between 2 and 5 h after injection. Pinocytosis at the distal small intestine seems the likely explanation for this difference, and this is supported by results of ileal injection of radioisotope in the suckling mice. 2. The distribution of 64 Cu in various organs was measured in suckling normal, mutant and heterozygote mice and in adult normal and mutant mice during 48 h after intracardiac injection. Excessive accumulation of radioisotope was observed in most extrahepatic organs of mutant and heterozygote mice and was most pronounced in kidney. This could not be explained by initial copper deficiency. The livers of suckling mutant and heterozygote mice lost radioisotope rapidly after normal initial uptake. This pattern was not seen in adult mutants.

scholarly journals Copper metabolism in mottled mouse (Mus musculus) mutants Studies of blotchy (Moblo) mice and a comparison with brindled (Mobr) mice

1981 ◽  
Vol 196 (1) ◽  
pp. 81-88 ◽  
Author(s):  
J R Mann ◽  
J Camakaris ◽  
N Francis ◽  
D M Danks
Keyword(s):  
Weight Gain ◽  
Normal State ◽  
Copper Metabolism ◽  
Dose Effect ◽  
Abnormal Distribution ◽  
Copper Distribution ◽  
Copper Therapy ◽  
The Difference ◽  
Lower Capacity ◽  
Very High

1. Copper concentrations were low in many organs of Moblo/Y mice, but very high in the gut. Absorption of 64Cu was seen to be very low when related to the absorption of cyano[57Co]cobalamin. The results in Moblo/+ mice were intermediate. 2. Copper therapy temporarily ameliorated many effects of the mutation in Moblo/Y mice, but did not improve the rate of weight gain as has been achieved previously in Mobr/Y mice. Lower capacity for a ‘depot dose’ effect at the site of injection may explain the difference. 3. The distribution of 64Cu after administration into the bloodstream of Moblo/Y mice altered from an initially normal state to one that resembled the abnormal distribution of pre-existing copper by 48 h. This indicated that the later mechanisms of copper distribution were at fault. Moblo/+ mice were equally affected. 4. The alteration of copper homoeostasis in blotchy mice was similar to that observed in brindled mice previously and in the present studies, although generally less severe. This is consistent with allelism of the two mutations.

Copper deficiency masquerading as myelodysplastic syndrome

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1493-1495 ◽  
Author(s):  
Xylina T. Gregg ◽  
Vishnu Reddy ◽  
Josef T. Prchal
Keyword(s):  
Myelodysplastic Syndrome ◽  
Copper Deficiency ◽  
Severe Neutropenia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Billroth Ii ◽  
Morphologic Characteristics ◽  
Red Blood Cell Transfusions ◽  
Copper Therapy ◽  
Stimulating Factor

We describe a woman with severe neutropenia and dependency on red blood cell transfusions who had previously undergone Billroth II surgery and whose bone marrow (BM) showed morphologic characteristics typical of myelodysplastic syndrome (MDS) with ringed sideroblasts. She had transient reversal of anemia and severe neutropenia after therapy with erythropoietin and granulocyte colony-stimulating factor. Because of relapse while receiving growth factors, the patient was referred for allogeneic BM transplantation. A pretransplantation nutritional evaluation revealed severe copper deficiency, and her hematologic abnormalities resolved fully with copper therapy. This case shows that copper deficiency should be an integral part of the differential diagnosis of sideroblastic MDS, even in patients not requiring parenteral nutrition.

scholarly journals Comparison of pathways of copper metabolism in aorta and liver. A functional test of metallothionein

1982 ◽  
Vol 204 (2) ◽  
pp. 541-548 ◽  
Author(s):  
J E Balthrop ◽  
C T Dameron ◽  
E D Harris
Keyword(s):  
Specific Activity ◽  
Soluble Fraction ◽  
Lysyl Oxidase ◽  
Copper Metabolism ◽  
Radioactive Isotopes ◽  
Zinc Binding ◽  
Aortic Tissue ◽  
Copper Binding ◽  
Liver Copper ◽  
Intracellular Metabolism

Soluble fractions from chick liver and aorta were examined for copper-binding proteins. In liver a zinc-binding thionein appeared to be the major binding protein for copper. Aortic tissue contained only traces of this thionein protein. Unlike liver, moderate amounts of soluble copper in aorta showed no association with macromolecules. Chicks fed on copper-deficient diets for 8 days had one-third the liver copper concentrations of controls. Aortic copper concentration was decreased only slightly, but the activity of lysyl oxidase, a copper-dependent enzyme in aorta, was decreased significantly. Treating the deficient chicks with CuSO4 (1 mg/kg) restored liver copper rapidly. The increase correlated with the binding of copper to a 10 000-mol.wt. component in the soluble fraction. Aortic copper concentrations responded much less to the CuSO4 treatment, but lysyl oxidase activity was again measurable in the tissue. Radioactive isotopes of copper bound almost exclusively to the 10 000-mol.wt. component in liver and to components of mol.wt. 30 000 or above in aorta. Hardly any of the administered radioactivity appeared with the 10 000-mol.wt. components in aorta, and none was found with unbound copper. The 30 000-mol.wt. components in aorta showed superoxide dismutase activity that was sensitive to NaCN. They also showed the highest specific activity of copper of any other aorta component. A clear distinction was seen between the metabolism of copper in liver and aortic tissues. Whereas a copper thionein, metallothionein, was a major component in the liver pathway, it is doubtful that this protein plays a major role in the intracellular metabolism of copper in aortic tissue.

The effect of molybdenum, sulphur and iron on the copper status of store lambs

2000 ◽  
Vol 2000 ◽  
pp. 88-88
Author(s):  
A.M. Mackenzie ◽  
S Evans ◽  
J.N.C. Lynn ◽  
D.V. Illingworth ◽  
R.G. Wilkinson
Keyword(s):  
Copper Deficiency ◽  
Clinical Signs ◽  
Copper Metabolism ◽  
Mineral Deficiency ◽  
Copper Status ◽  
Biochemical Indicator ◽  
Copper Supplementation ◽  
The World ◽  
Plasma Copper ◽  
Accurate Indicator

Clinical copper deficiency is the second most common mineral deficiency in the world, the main cause being high dietary levels of molybdenum, sulphur and iron. Phillippo et al, (1987) reported that clinical signs of deficiency resulted from high dietary Mo and S. However, Fe and S resulted in hypocupraemia but did not induce clinical signs of deficiency. Therefore is was concluded that clinical copper deficiency was due to a direct effect of dietary Mo and S on copper metabolism in ruminants. Mackenzie et al. (1997) reported that plasma copper levels were not an accurate indicator of copper status and unlikely to predict animals requiring copper supplementation. Caeruloplasmin is large copper enzyme and accounts for 88% of plasma copper and Mackenzie et al. (1997) proposed that a caeruloplasmin to plasma copper ratio may provide a more accurate biochemical indicator of copper status. This trial was designed to investigate the effect of dietary Mo, S and Fe on the copper status of the lambs.

scholarly journals Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice

Science ◽  
2020 ◽  
Vol 368 (6491) ◽  
pp. 620-625 ◽  
Author(s):  
Liam M. Guthrie ◽  
Shivatheja Soma ◽  
Sai Yuan ◽  
Andres Silva ◽  
Mohammad Zulkifli ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Small Molecule ◽  
Murine Model ◽  
Copper Deficiency ◽  
Menkes Disease ◽  
Neurological Injury ◽  
Loss Of Function ◽  
Brindled Mouse ◽  
The Brain

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse—a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency.

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