Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the molecular basis of dosage compensation in Drosophila, a recombinant lambda phage containing the Drosophila melanogaster glucose-6-phosphatase dehydrogenase (G6PD) gene was isolated by differential screening of a Drosophila genomic lambda library with poly(A)+RNA obtained from polyribosomes enriched for or depleted of G6PD mRNA sequences. Of 44 000 plaques screened, a single phage, lambda DmG21, showed hybridization with the enriched poly(A)+RNA but not the depleted one. Confirmation that the Drosophila DNA fragment cloned in lambda DmG21 contains the G6PD gene sequence is based on the following observations. lambda DmG21 DNA shows hybridization only to the 18D region of the salivary gland X-chromosome, which is the known cytological locus for the G6PD gene. In vitro translation of the poly(A)+mRNA selected by hybridization to lambda DmG21 DNA sequences shows a polypeptide product of apparent Mr 55 000, identical to that of the monomeric unit of G6PD. When the putative coding sequence of G6PD is cloned into the expression vector lambda gt11, recombinant plaques are recognized by anti-G6PD immunoglobulin. A transcriptional map of the G6PD gene shows that it is divided into two exons, 0.9 kb (exon I) and 1.8 kb (exon II) long, which are separated by a 2.4-kb intron. The G6PD mRNA is 2.0 kb in length and the steady-state level of the mRNA is similar in both sexes. Measurement of the copy number of the G6PD gene in males and females shows the gene to be present once per X-chromosome in both sexes. No amplification of the gene sequence was observed in males. These results are, therefore, in agreement with the previous suggestion that dosage compensation is the result of enhanced transcription of X-linked genes in males.
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PMID:Isolation and characterization of the glucose-6-phosphate dehydrogenase gene of Drosophila melanogaster. 316 84

Connexin32 (Cx32) is the major gap junctional protein in mouse liver. We have shown recently that the formation of liver tumours in Cx32-deficient mice is strongly increased in comparison with control wild-type mice, demonstrating that the deficiency in gap junctional communication has an enhancing effect on hepatocarcinogenesis. We have now compared the effect of Cx32 deficiency on liver carcinogenesis in two strains of mice with differing susceptibility to hepatocarcinogenesis. Heterozygous Cx32(+/-) females were crossed with male Cx32 wild-type C57BL/6J (low susceptibility) or C3H/He (high susceptibility) mice. Since the Cx32 gene is located on the X-chromosome, the resulting F1 males segregated to the genotypes Cx32(Y/+) and Cx32(Y/-). Genotyping was performed by PCR-analysis using tail-tip DNA. Weanling male mice were i.p. injected with a single dose of N-nitrosodiethylamine and were killed 16, 21 or 26 weeks later. The number, volume fraction and size distribution of precancerous liver lesions characterized by a deficiency in the marker enzyme glucose-6-phosphatase were quantitated. The results demonstrate that Cx32 deficiency only slightly affects the number of enzyme-altered lesions, but strongly enhances their growth, both in the resistant and the susceptible mouse strain, suggesting that decreased intercellular communication results in tumour promoting activity irrespective of the genetic background of the mouse strain used. Since Cx32-deficient C3H/He hybrids were approximately 5-10 times more sensitive than C3H/He hybrids with an intact Cx32 gene, this mouse strain may prove very useful for toxicological screening purposes.
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PMID:The effect of connexin32 null mutation on hepatocarcinogenesis in different mouse strains. 1038 16

Mice deficient for connexin32 (Cx32), the major gap junction forming protein in liver, are highly susceptible to hepatocarcinogenesis. Because the Cx32 gene is located on the X-chromosome, heterozygous females show mosaicism with respect to Cx32 expression; this enables their use in studying the effect of Cx32-deficiency in a mixed Cx32-plus/Cx32-minus environment in vivo. Female C3H/He mice (Cx32(+/+)) were crossed with Cx32-deficient C57BL/129Sv males (Cx32(Y/-)) to yield F1 females heterozygous with respect to Cx32 (Cx32(+/-)). Patches of hepatocytes were observed in normal liver that either expressed Cx32 or failed to express the protein. The mean fraction of Cx32-negative tissue in liver was about 60% and did not change significantly with age of mice. Neoplastic liver lesions, induced in weanling mice, were identified in serial liver sections by their deficiency in glucose-6-phosphatase staining. Parallel sections were used for immunohistochemical demonstration of Cx32 protein. Smaller lesions were either homogenously Cx32-negative or showed unchanged to slightly elevated levels of Cx32 protein. There were no major differences in number and size distribution between lesions of these 2 phenotypes. In addition, larger lesions were mostly Cx32-negative but often contained embedded patches of Cx32-positive cells. Staining for the proliferation-associated nuclear antigen Ki-67 did not reveal significant differences between Cx32-negative and Cx32-positive hepatocytes in Cx32-mosaic tumors. This suggests that expression of Cx32 within a subpopulation of tumor cells does not negatively regulate their growth nor does it seem to affect the proliferation of their directly neighboring Cx32-negative counterparts.
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PMID:Hepatocarcinogenesis in female mice with mosaic expression of connexin32. 1096 Apr 41