Biomaterial Database

Correction of a genetically caused enzyme defect by somatic cell hybridization. 1983

C F Cori, and S Gluecksohn-Waelsch, and P A Shaw, and C Robinson

Liver cells obtained from newborn mice homozygous for any one of several overlapping deletions in chromosome 7 fail to express a number of liver-specific differentiated traits. Among these is the activity of the membrane-bound liver-specific enzyme glucose-6-phosphatase (Glc-6-Pase; D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9). Previous studies have led to the suggestion that the region of the genome covered by these deletions includes genes that normally regulate the expression of structural genes encoding liver-specific enzymes and proteins mapping elsewhere in the genome. To find out whether the deficiency of Glc-6-Pase may be caused by the deletion of the relevant structural gene, mouse liver cells homozygous for the deletion c14CoS were hybridized with 2S Faza rat hepatoma cells, and the hybrid cell cultures were analyzed for mouse and rat Glc-6-Pase activity. Hybrids showed expression of mouse Glc-6-Pase activity, proving that the structural gene for this enzyme is not included in the deletion c14CoS in chromosome 7. In the hybrid cells the rat hepatoma genome apparently contributes a factor that activates the structural gene of the mouse and corrects its failure of expression, which most likely resulted from the deletion of an essential regulatory or processing gene. By using as a marker glucose-6-phosphate isomerase (Glc-6-PIase; glucosephosphate isomerase, D-glucose-6-phosphate ketolisomerase, EC 5.3.1.9), known to map on chromosome 7, this entire chromosome could be excluded as a possible carrier of the Glc-6-Pase structural gene. In addition, the structural genes for Glc-6-Pase and for tyrosine aminotransferase (TyrATase; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), another enzyme deficient in lethal deletion homozygotes, were shown to map on two different chromosomes. Together with our previous studies of TyrATase gene regulation, the present experiments suggest that the region of the mouse genome defined by the deletions includes one or more genes regulating the expression of several structural genes that map on different chromosomes and that encode liver-cell-type specific traits.

UI	MeSH Term	Description	Entries
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008114	Liver Neoplasms, Experimental	Experimentally induced tumors of the LIVER.	Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008817	Mice, Mutant Strains	Mice bearing mutant genes which are phenotypically expressed in the animals.	Mouse, Mutant Strain,Mutant Mouse Strain,Mutant Strain of Mouse,Mutant Strains of Mice,Mice Mutant Strain,Mice Mutant Strains,Mouse Mutant Strain,Mouse Mutant Strains,Mouse Strain, Mutant,Mouse Strains, Mutant,Mutant Mouse Strains,Mutant Strain Mouse,Mutant Strains Mice,Strain Mouse, Mutant,Strain, Mutant Mouse,Strains Mice, Mutant,Strains, Mutant Mouse
D002872	Chromosome Deletion	Actual loss of portion of a chromosome.	Monosomy, Partial,Partial Monosomy,Deletion, Chromosome,Deletions, Chromosome,Monosomies, Partial,Partial Monosomies
D002874	Chromosome Mapping	Any method used for determining the location of and relative distances between genes on a chromosome.	Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D005796	Genes	A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.	Cistron,Gene,Genetic Materials,Cistrons,Genetic Material,Material, Genetic,Materials, Genetic
D005809	Genes, Regulator	Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.	Gene, Regulator,Regulator Gene,Regulator Genes,Regulatory Genes,Gene, Regulatory,Genes, Regulatory,Regulatory Gene
D005953	Glycogen Storage Disease Type I	An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.	Glucose-6-Phosphatase Deficiency,Glucosephosphatase Deficiency,Glycogenosis 1,Hepatorenal Glycogen Storage Disease,von Gierke Disease,Deficiency, Glucosephosphatase,Gierke Disease,Gierke's Disease,Glycogen Storage Disease 1 (GSD I),von Gierke's Disease,Deficiencies, Glucose-6-Phosphatase,Deficiencies, Glucosephosphatase,Deficiency, Glucose-6-Phosphatase,Disease, Gierke,Disease, Gierke's,Disease, von Gierke,Disease, von Gierke's,Gierkes Disease,Glucose 6 Phosphatase Deficiency,Glucose-6-Phosphatase Deficiencies,Glucosephosphatase Deficiencies,von Gierkes Disease
D006822	Hybrid Cells	Any cell, other than a ZYGOTE, that contains elements (such as NUCLEI and CYTOPLASM) from two or more different cells, usually produced by artificial CELL FUSION.	Somatic Cell Hybrids,Cell Hybrid, Somatic,Cell Hybrids, Somatic,Cell, Hybrid,Cells, Hybrid,Hybrid Cell,Hybrid, Somatic Cell,Hybrids, Somatic Cell,Somatic Cell Hybrid