scholarly journals The relationship of excess copper accumulation by fibroblasts from the brindled mouse model of Menkes disease to the primary defect

1990 ◽  
Vol 267 (2) ◽  
pp. 417-422 ◽  
Author(s):  
G L Waldrop ◽  
M J Ettinger
Keyword(s):  
Mouse Model ◽  
Menkes Disease ◽  
Cell Types ◽  
Copper Accumulation ◽  
Primary Defect ◽  
Excess Copper ◽  
Brindled Mouse ◽  
Copper Zinc ◽  
Relationship Of ◽  
Brindled Mice

Fibroblasts from the brindled mouse model of Menkes disease are known to accumulate excess copper. Most of the copper in the cytosol of these fibroblasts is bound to metallothionein (MT), which is elevated in Menkes or brindled mouse fibroblasts. Copper accumulation by normal fibroblasts containing excess MT was examined to determine if the excess copper accumulation phenotype was secondary to excess MT or associated with the primary defect in fibroblasts from the brindled mice. MT was induced in normal fibroblasts by copper, zinc or dexamethasone to levels comparable with those in brindled mice fibroblasts, as determined by radioimmunoassays. Normal fibroblasts containing excess MT accumulate copper normally, i.e. they do not exhibit the excess copper accumulation phenotype. Consistent with this result, copper efflux from normal fibroblasts containing excess MT was also normal. The data suggest that one function of the protein associated with the primary defect is to help determine how much copper is taken up and retained by fibroblasts and other cell types exhibiting the excess copper phenotype in Menkes disease. The capacity of this protein is apparently exceeded in normal fibroblasts if serum or albumin is not present extracellularly to limit total copper uptake. Consistent with a defect in an intracellular protein, the kinetics of copper transport by brindled mice fibroblasts were found to be normal.

scholarly journals Effects of dietary copper deficiency on male offspring of heterozygous brindled mice

1989 ◽  
Vol 62 (1) ◽  
pp. 177-184
Author(s):  
Joseph R. Prohaska
Keyword(s):  
Copper Deficiency ◽  
Menkes Disease ◽  
Male Offspring ◽  
Dietary Copper ◽  
Cu Deficiency ◽  
C57bl Mice ◽  
Brindled Mouse ◽  
Normal Males ◽  
Cell Volumes ◽  
Brindled Mice

Female C57BL mice heterozygous for the brindled gene were mated to normal males and fed on a purified diet low in copper throughout gestation and lactation with (+ Cu) or without (−Cu) Cu-supplemented drinking water. Male offspring of two genotypes (control, + /y and brindled, Mobr/y) were compared when 10–12 d old. Brindled mice from dams on the – Cu treatment were smaller and had lower packed cell volumes than brindled mice from dams on the + Cu treatment. The −Cu brindled mice were smaller than their littermate brothers (+/y) but had equivalent biochemical features consistent with severe Cu deficiency. Compared with control mice from dams on the +Cu treatment, caeruloplasmin (EC1.16.3.1) activity was lower in offspring of all three other groups including Mobr/y mice who were not anaemic. Iron levels were similar in organs and bone marrow from all four groups of offspring. When dietary Cu is limiting in brindled mice a more severe Cu deficiency ensues. Thus, appropriate Cu nutriture is important to the management of Menkes' disease in humans, a genetic analogue of the brindled mouse.

The Female Brindled Mouse as a Model of Menkes' Disease: The Relationship of Fur Pattern to Behavioral and Neurochemical Abnormalities

1991 ◽  
Vol 13 (3) ◽  
pp. 121-129 ◽  
Author(s):  
Parthena M. Martin ◽  
Mika Irino ◽  
Kinuko Suzuki ◽  
Mark H. Lewis ◽  
Richard B. Mailman
Keyword(s):  
Menkes Disease ◽  
Brindled Mouse ◽  
Relationship Of ◽  
The Relationship

scholarly journals Metabolomic Analyses Reveal Extensive Progenitor Cell Deficiencies in a Mouse Model of Duchenne Muscular Dystrophy

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 61 ◽  
Author(s):  
Josiane Joseph ◽  
Dong Cho ◽  
Jason Doles
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Progenitor Cell ◽  
Treatment Options ◽  
Cell Types ◽  
Mdx Mouse ◽  
Mdx Mice ◽  
Metabolic Alterations ◽  
Potential Contributor

Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

Functional analysis of a genetic defect of copper transport (Menkes disease) in different cell lines

1996 ◽  
Vol 271 (1) ◽  
pp. C378-C384 ◽  
Author(s):  
Y. Qian ◽  
E. Tiffany-Castiglioni ◽  
E. D. Harris
Keyword(s):  
Genetic Defect ◽  
Menkes Disease ◽  
Cell Types ◽  
Polymerase Chain Reaction Analysis ◽  
C6 Glioma Cells ◽  
C6 Cells ◽  
Bewo Cells ◽  
Before And After ◽  
Base Pair Fragment ◽  
Different Cell Types

To define the function of the Cu-transporting ATPase in Menkes disease, Menkes and normal fibroblasts were incubated with 67Cu before and after brief exposure to -SH reagents, p-chloromercuribenzoate (PCMB) and dithiothreitol (DTT). Accumulation and retention were compared among these cells, BeWo cells, and rat C6 glioma cells similarly treated. The Michaelis constant for influx of 67Cu into normal and Menkes fibroblasts was practically the same (0.21 +/- 0.07 vs. 0.24 +/- 0.06 microM). The PCMB treatment stimulated 67Cu accumulation in C6 cells, inhibited accumulation in normal and Menkes fibroblasts, and did not affect BeWo cells. DTT stimulated 67Cu uptake in all cells but BeWo cells. DTT treatment after PCMB further enhanced 67Cu accumulation in normal fibroblasts and C6 cells but had no enhancing effect on Menkes fibroblasts or BeWo cells. Menkes fibroblasts and BeWo cells released 67Cu at rates considerably slower than normal fibroblasts (0.06 and 0.09 vs. 0.22%/min, respectively). The PCMB blocked 67Cu release from normal fibroblasts but did not affect Menkes fibroblasts or BeWo cells. Reverse transcription-polymerase chain reaction analysis of total RNA from BeWo cells failed to show a predicted 943-base pair fragment representing a partial transcript of the Menkes factor. The fragment was present in extracts from normal fibroblasts. We conclude that the mechanism underlying Cu homeostasis varies among different cell types. As exemplified by BeWo and Menkes cells, failure to efflux Cu ions may be linked with the failure to express a functional Cu-transporting ATPase, namely, the Menkes protein.

scholarly journals A new mouse model to study restoration of interleukin-6 (IL-6) expression in a Cre-dependent manner: microglial IL-6 regulation of experimental autoimmune encephalomyelitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Paula Sanchis ◽  
Olaya Fernández-Gayol ◽  
Gemma Comes ◽  
Kevin Aguilar ◽  
Anna Escrig ◽  
...  
Keyword(s):  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Interleukin 6 ◽  
Clinical Symptoms ◽  
Recovery Of Function ◽  
Cell Types ◽  
Dependent Manner ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Abstract Background Interleukin-6 (IL-6) is a pleiotropic cytokine that controls numerous physiological processes both in basal and neuroinflammatory conditions, including the inflammatory response to experimental autoimmune encephalomyelitis (EAE). IL-6 is produced by multiple peripheral and central cells, and until now, the putative roles of IL-6 from different cell types have been evaluated through conditional cell-specific IL-6 knockout mice. Nevertheless, these mice probably undergo compensatory responses of IL-6 from other cells, which makes it difficult to assess the role of each source of IL-6. Methods To give some insight into this problem, we have produced a novel mouse model: a conditional reversible IL-6 KO mouse (IL6-DIO-KO). By using double-inverted, open-reading-frame (DIO) technology, we created a mouse line with the loss of Il6 expression in all cells that can be restored by the action of Cre recombinase. Since microglia are one of the most important sources and targets of IL-6 into the central nervous system, we have recovered microglial Il6 expression in IL6-DIO-KO mice through breeding to Cx3cr1-CreER mice and subsequent injection of tamoxifen (TAM) when mice were 10–16 weeks old. Then, they were immunized with myelin oligodendrocyte glycoprotein 35-55 peptide (MOG35-55) 7 weeks after TAM treatment to induce EAE. Clinical symptoms and demyelination, CD3 infiltration, and gliosis in the spinal cord were evaluated. Results IL6-DIO-KO mice were resistant to EAE, validating the new model. Restoration of microglial Il6 was sufficient to develop a mild version of EAE-related clinical symptoms and neuropathology. Conclusions IL6-DIO-KO mouse is an excellent model to understand in detail the role of specific cellular sources of IL-6 within a recovery-of-function paradigm in EAE.

scholarly journals Incidence of the Common Forms of Human Leukemia

Blood ◽  
1956 ◽  
Vol 11 (10) ◽  
pp. 871-881 ◽  
Author(s):  
BRIAN MACMAHON ◽  
DUNCAN CLARK
Keyword(s):  
White Cell Count ◽  
Cell Types ◽  
Human Leukemia ◽  
Death Certificates ◽  
Hospital Records ◽  
White Males ◽  
Lymphatic Leukemia ◽  
Younger Age ◽  
Relationship Of ◽  
Two Populations

Abstract From hospital records and from death certificates, an attempt was made to assemble data on all residents of the Borough of Brooklyn diagnosed as having leukemia in the period 1943-52. A total of 1792 abstracts of hospital records and 1830 death certificates gave information on 1709 patients. The mean Brooklyn population over the same period is used to express incidences of the various forms of leukemia in relation to color, sex and age. The incidence of leukemia in white males and females was 71.3 and 57.7 per million per annum respectively. Corresponding rates for Negroes were 46.5 and 30.6. The white-Negro difference was decreased but not eliminated by standardization to allow for differences in the age distributions of the two populations. Sex ratios were lower for the acute forms of the disease than for the chronic forms, and, in both acute and chronic forms, for myeloid than for lymphatic cell types. No relationship of sex ratio with age at diagnosis or initial white cell count was found. Each pathologic variety of leukemia has its own distinct age incidence curve. The lymphatic forms appear to be more sharply associated with the extremes of life than do the myeloid varieties. That is, acute lymphatic leukemia appears at a younger age than does acute myeloid leukemia and the chronic lymphatic form appears at an older average age than the chronic myeloid variety.

scholarly journals Imaging Tolerance Induction in the Classic Medawar Neonatal Mouse Model: Active Roles of Multiple F1-Donor Cell Types

2015 ◽  
Vol 15 (9) ◽  
pp. 2346-2363 ◽  
Author(s):  
R. A. Bascom ◽  
K. S. Tao ◽  
S. L. Tollenaar ◽  
L. J. West
Keyword(s):  
Mouse Model ◽  
Tolerance Induction ◽  
Donor Cell ◽  
Cell Types ◽  
Neonatal Mouse
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