Disease relevance of Ros1

• The human homolog, c-ros, of the transforming gene, v-ros, of the avian sarcoma virus, UR2, has been isolated from a human genomic library [1].
• The infertility of c-ros knockout male mice can be explained by the sperm's inability to enter the oviduct, as a result of their bent tails forming the entangled sperm mass and their compromised flagellar vigor within the uterus [2].
• Transgenic mice with male infertility, the c-ros knockout (KO) and GPX5-Tag2 transgenic mouse models, are compared [3].
• Analysis yielded 20 novel genes differentially expressed in both lung adenomas and ACs versus normal lungs, including the tumor suppressor APC2 and the oncogene Ros 1 [4].

High impact information on Ros1

• The primary defect in the mutant animals was located in the epididymis, showing that c-ros controls appropriate development of the epithelia, particularly regionalization and terminal differentiation [5].
• The c-ros gene was originally identified in mutant form as an oncogene [5].
• The c-ros tyrosine kinase receptor controls regionalization and differentiation of epithelial cells in the epididymis [5].
• We demonstrate that c-ros is not required in a cell autonomous manner for male germ cell development or function [5].
• The human c-ros gene (ROS) is located at chromosome region 6q16----6q22 [1].

Chemical compound and disease context of Ros1

• The cause of infertility of male c-ros tyrosine kinase receptor knockout mice [2].

Biological context of Ros1

• The glutamate transporter-associated protein (GTRAP) 3-18 was detected in all epididymal regions independent of genotype, but a highly abundant novel transcript of 4.2 kilobases was found only in the initial segment of heterozygous c-ros mice [6].
• Thus, the c-ros gene joins the c-myb oncogene, which is distal to the c-ros gene on the long arm of human chromosome 6, as a candidate for involvement in chromosome 6q deletions and rearrangements seen in various malignancies [1].
• The c-ros proto-oncogene is the vertebrate homologue of the Drosophila sevenless tyrosine kinase receptor [7].
• The c-ros tyrosine kinase receptor may provide a signal transduction pathway for epithelial-mesenchymal interactions [7].
• The temporal and spatial arrangement of c-ros transcripts is coincident with the phenotypic induction and proliferation of epithelium during organogenesis of the kidney and intestine [7].

Anatomical context of Ros1

• Gene and protein expression in the epididymis of infertile c-ros receptor tyrosine kinase-deficient mice [8].
• A single-copy fragment from the human c-ros genomic clone has been used to map the human c-ros homolog (ROS) to human chromosome region 6q16----6q22 by somatic cell hybrid analysis and chromosomal in situ hybridization [1].
• Lipid diffusion in the plasma membrane of mouse spermatozoa: changes during epididymal maturation, effects of pH, osmotic pressure, and knockout of the c-ros gene [9].
• The maintenance of the full complement of epithelia in the murine caput epididymidis in the adult thus requires a combination of luminal fluid from the testis, tissue DHT and the presence of the c-ros oncogene [10].
• The role of these receptors and c-ros, a receptor-type kinase expressed on the tip of the ureter bud, was studied by modified antisense oligonucleotides [11].

Associations of Ros1 with chemical compounds

• Development of the caput epididymidis studied by expressed proteins (a glutamate transporter, a lipocalin and beta-galactosidase) in the c-ros knockout and wild-type mice with prepubertally ligated efferent ducts [12].
• Transgenic mice targeted for the c-ros gene, which are fertile when heterozygous (HET), but infertile when homozygous (knockout, KO) and associated with failure in pubertal differentiation of the epididymal initial segment, provide a model for studying the role of the epididymal luminal environment in sperm development [13].
• Thus, caput region I develops before c-ros expression, high testosterone secretion and differentiation of regions II and III but not if the organ is deprived of the oncogene c-ros or testicular exocrine secretions [12].
• Comparative role of phosphotyrosine kinase domains of c-ros and c-ret protooncogenes in metanephric development with respect to growth factors and matrix morphogens [14].
• Expression and location of taurine transporters and channels in the epididymis of infertile c-ros receptor tyrosine kinase-deficient and fertile heterozygous mice [15].

Other interactions of Ros1

• Lack of glutamate transporter EAAC1 in the epididymis of infertile c-ros receptor tyrosine-kinase deficient mice [6].
• Snx3, and Ros1 [16].
• Additionally, three genes (Ros1, Grik2, and Zfa) were eliminated as possible candidates for vAlb, and several SSLP markers were separated genetically [17].
• Cloning of mouse c-ros renal cDNA, its role in development and relationship to extracellular matrix glycoproteins [18].

Analytical, diagnostic and therapeutic context of Ros1

• Competitive RT-PCR analyses revealed the c-ros expression was the highest at 13th day of gestation, and it declined to very low levels during the neonatal period [18].
• Analysis by cDNA microarrays showed that in the murine epididymis, NaPi-IIb was the predominantly expressed epithelial isoform of the sodium-inorganic phosphate cotransporter and was markedly overexpressed in the proximal region in the infertile knockout (KO) compared to the fertile heterozygous (HET) c-ros transgenic mouse [19].
• The role of various receptor-like protooncogenes, with the emphasis on c-ros and c-ret, was investigated by antisense-oligodeoxynucleotide (ODN) gene-targeting strategies at a point in metanephric development when reciprocal-inductive interactions between the epithelium and mesenchyme have already been initiated and are rampant [14].
• Real-time PCR analysis showed that c-ros mRNA is expressed all along the human epididymis with the exception of the proximal caput epididymidis, where c-ros transcript was undetectable [20].

References