The Drosophila melanogaster RPS17 gene encoding ribosomal protein S17

A human ribosomal protein S17 cDNA [Chen et al., Proc. Natl. Acad. Sci. USA 83 (1986) 6907-6911] was used as heterologous probe to isolate S17 clones from Drosophila genomic and cDNA recombinant libraries. Five S17 genomic clones were recognized; all contained overlapping regions of a single chromosomal site. Subsequently the Drosophila RPS17 gene was mapped by in situ hybridization to chromosome 3L, band 67B1-5. The locus spans approximately 1000 bp of DNA and includes four exons. It is preceded by conventional CAAT and TATA RNA polymerase II promoter motifs. The 131 amino acid protein encoded within Drosophila RPS17 is similar to ribosomal proteins from several other eukaryotes. Comparison of eukaryotic S17 proteins' primary structures as well as the number and location of their genes' intervening sequences suggest that S17 is a relatively recent addition to the ribosomal protein family, probably post-dating divergence of eukaryotes and prokaryotes.     

Regulation of the gene for estrogenic 17-ketosteroid reductase lying on chromosome 17cen----q25

17-Ketosteroid reductase (17KSR), also known as 17 beta-hydroxysteroid dehydrogenase, catalyzes the reversible interconversion of estradiol to estrone and of androstenedione to testosterone. Using a recently cloned human placental 17KSR cDNA, we show that the 1.4-kilobase mRNA for this enzyme is detected only in tissues producing estrogens, and a 2.4-kilobase mRNA is detected in some estrogenic tissues and some androgenic tissues. This tissue distribution suggests that the interconversion of androstenedione and testosterone may be mediated by a different enzyme. Southern blotting studies show that the mRNA for this estrogenic 17KSR is encoded by two very similar genes localized to chromosome 17cen----q25 by analysis of DNA from mouse/human somatic hybrid cell lines. 8-Br-cAMP increases the abundance of estrogenic 17KSR mRNA as well as mRNAs for other steroidogenic enzymes in JEG-3 choriocarcinoma cells. By contrast, cAMP decreases estrogenic 17KSR mRNA in primary cultures of human cytotrophoblasts and human granulosa cells, a pattern of tropic regulation that differs from other steroidogenic enzyme mRNAs.     

17Beta-estradiol decreases hypoxic induction of erythropoietin gene expression

Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17beta-estradiol (E2-beta) inhibits this effect. We hypothesized that E2-beta decreases EPO gene expression during hypoxia. Because E2-beta can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-beta inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-beta (20 microg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O(2)) or normoxia. We found that E2-beta treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-beta treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-beta decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.     

Tau gene mutations: dissecting the pathogenesis of FTDP-17

Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. Abnormal filamentous tau deposits constitute a major defining characteristic of several neurodegenerative diseases, including Alzheimer's disease. Although the presence of tau pathology correlates with the symptoms of Alzheimer's disease, there was no genetic evidence linking tau to neurodegeneration until recently. However, since 1998, the identification of more than 25 mutations in the tau gene, associated with frontotemporal dementia and parkinsonism linked to chromosome 17, has demonstrated that tau dysfunction can lead to neurodegeneration and the development of clinical symptoms.     

Mapping of the L-methylmalonyl-CoA mutase gene to mouse chromosome 17

In humans, methylmalonyl acidemia is caused by a deficiency of L-methylmalonyl-CoA mutase (MUT) controlled by a gene that has been mapped to chromosome 6. The mouse homolog of this gene has now been mapped to mouse chromosome 17. Recombinant inbred and congenic strains place the mouse Mut locus 1.06 cM distal to H-2, between Pgk-2 and Ce-2. The relative order of syntenic probes flanking H-2 on mouse chromosome 17 and HLA on human chromosome 6 is shown to be different.