Enzyme changes associated with mitochondrial malic enzyme deficiency in mice

Mohrenweiser, Harvey W.; Erickson, Robert P.

doi:10.1016/0304-4165(79)90435-5

Cited by 4 publications

(4 citation statements)

References 33 publications

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“…Additional regulatory activity appears to reside in another region of the C3H deletion and to concern as yet unidentified biochemical functions that are normal in cI4CoS homozygotes but deficient in C3H homozygotes. Previous studies of mice carrying both the C3H and C6H deletions, the latter partially complementing the c3H deletion (1), have shown these mice to have increased glycolytic and transaminase enzyme activities, suggesting the control of more than one regulatory mechanism by the relevant region of chromosome 7 (17,18). Further analysis of the regulatory genes included in the albino deletions and of their effects is expected to contribute to the understanding of mechanisms of developmental regulation of prenatal gene differentiation.…”

Section: Resultsmentioning

confidence: 99%

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

Giometti

Gemmell

Taylor

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, eH and e4cos, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cck/^cc), heterozygous (Cch/C'H or Ce/CI4coS), and deletion homozygous (c3H/c3H or c14cos/c14cos) mice. Livers offetal and newborn c'f heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of eH homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c" homozygotes. Livers of fetal and newborn mice homozygous for the 4CoS deletion, which overlaps the eH deletion and produces a similar phenotype, expressed normal amounts ofthese proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the e" but not the c14s deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c-H and c1os deletions.

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Section: Resultsmentioning

confidence: 99%

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

Giometti

Gemmell

Taylor

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…A 4-fold increase in liver glucose-6-phosphate dehydrogenase is associated with a 2-fold increase in 6-phosphogluconate dehydrogenase activity in livers of C3H/C6H mice (5). Also, while mitochondrial malic enzyme activity is absent, the cytoplasmic enzyme is increased compared to littermate controls (5).…”

Section: Methodsmentioning

confidence: 99%

“…Other enzymes showing substantial reduction or complete absence of activity in affected mice have been associated with various lethal albino deletions (2). Additionally, a number of enzymes show an increase in activity, apparently in response to an altered metabolic state (5).…”

mentioning

confidence: 99%

Mice homozygous for chromosomal deletions at the albino locus region lack specific polypeptides in two-dimensional gels.

Baier¹,

Hanash²,

Erickson³

1984

Proc. Natl. Acad. Sci. U.S.A.

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Radiation-induced chromosomal deletions involving the albino locus region of the mouse result, when homozygous, in abnormalities ranging from sterility to lethality at various stages of development. We have utilized two-dimensional electrophoresis to search for polypeptide alterations in livers from newborn mice homozygous for the c14Cos and c3" deletions and also from C3H/C6H compound heterozygote mice. Five-hundred MATERIALS AND METHODS Material. The albino locus (c) in chromosome 7 originally served as a probe for the specific locus mutation-rate experiments on the mouse at the Oak Ridge National Laboratory, Oak Ridge, TN (7), and at the Medical Research Council Radiobiology Unit, Harwell, England (8). Three deletions spanning this locus were obtained for our study. The cl4CoS deletion (Oak Ridge) and the c3H deletion (Harwell) are lethal in the newborn period. The c6H deletion (Harwell) is lethal at the egg-cylinder stage. For our study, the c6H strain was used in crosses to the c3H strain to generate compound heterozygotes, c3H/c6H, which can survive to adulthood although they tend to be sterile (3).The currently accepted representation of the three deletions involved in this study is given in Fig. 1. The lethality of these deletions in homozygous mice necessitates their maintenance in the heterozygous state. Heterozygote brothersister matings produce three genotypes for analysis. cch/cD x cch/cD crosses result in cch/cch, cch/cD, and cD/cD mice, in which cD represents a lethal albino deletion. The various mutant strains are not congenic; each strain has been separately inbred for at least 40 generations (2).Heterozygotes for the deletions are distinguished from homozygous normal mice because the deletions are carried with the chinchilla allele (cch). Homozygotes for this allele have a darker skin color than do heterozygotes and thus heterozygotes can be mated inter se to maintain the line. At birth, the homozygotes for chinchilla are difficult to distinguish from heterozygotes for the deletions. In some of these strains, the eye will appear darker in the chinchilla homozygotes, but this is a somewhat subjective determination.Thus, pigmented littermates could be either cch/cch or heterozygotes for chinchilla with whatever lethal albino deletion is being considered. Since these pigmented littermates include two genotypes, they are denoted by the symbol Cch/c*, in which * stands for either chinchilla or a lethal albino deletion.2-DE. Mice were sacrificed within a few hours after birth.Livers were stored at -80°C for subsequent analysis.

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“…Mitochondrial malic enzyme deficiency occurs in mice with small deletions of the albhm region of chromosome 7 (Eicher et al, 1978;Mohrenweiser and Erickson, 1979). As several loci are likely to be deleted and several enzymes are affected in these strains, their use as a model of a specific enzyme deficiency must be severely limited (Bulfield, 1980).…”

Section: Carbohydrate Metabolismmentioning

confidence: 99%

Inherited metabolic disease in laboratory animals: a review

Bulfield

1980

J of Inher Metab Disea

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Research on the screening for and study of animal models of inherited metabolic disease is reviewed. It is emphasized that an animal model, to be of value, must be an inherited deficiency of the same enzyme as the one deficient in the human syndrome. If this criterion is adhered to there is a remarkable identity in aetiology between animal and man. Specific examples of inherited metabolic disease in laboratory animals are described for: amino acid metabolism; lysosomal storage diseases, carbohydrate metabolism, transport disorders and trace element metabolism; the mutants found in mice being the easiest to manipulate biochemically and genetically. There is still a lack of adequate screening programmes for animal homologues of the more serious human inborn errors (such as lysosomal storage diseases) where laboratory studies could provide significant advances in therapy.

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Enzyme changes associated with mitochondrial malic enzyme deficiency in mice

Cited by 4 publications

References 33 publications

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

Mice homozygous for chromosomal deletions at the albino locus region lack specific polypeptides in two-dimensional gels.

Inherited metabolic disease in laboratory animals: a review

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