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Related post: represent a wild mouse polymorphism of the MCF MuLV receptor determinant. (Kozak). Molecular mechanisms of leukemogenesis by Friend MuLV . In analyzing proviral insertions in Friend (F) murine leukemia virus (MuLV) induced tumors, a common proviral integration region for this retrovirus in -^10% of lymphoid and myeloid ieukemias was discovered. This integration region maps to mouse chromosome 7 very near a common integration region (Int-2 ) for mouse mammary tumor virus in mammary carcinomas. This integration region may represent a new oncogene or, alternatively, could indicate that the Int-2 locus is involved in lymphoid and myeloid Ieukemias as well as mammary carcinoma. The human equivalent of this integration site is presently being cloned and rearrangements or abnormal expression of this locus in human malignancies are being evaluated. (Silver) New DNA probes specific for MCF and xenotropic MuLV env sequences have been developed . DNA segments (100 bp) from analogous portions of the MCF and xenotropic gp70 env coding regions were isolated and subcloned into a M13 phage vector. No cross-reactivity could be demonstrated in Southern blot hybridizations of cloned xenotropic or MCF proviral DNAs. The labeled env- specific DNAs did not react with ecotropic or amphotropic MuLV sequences. We have previously shown that multiple copies of MuLV proviral DNA are present in mouse chromosomal DNA. An analysis of DNA prepared from a broad range of inbred mice indicated that many more endogenous provi ruses with a MCF env than ones with a xenotropic MuLV env segment exist in the mouse genome. Wild mouse strains were more diverse. Some had neither MCF nor xenotropic MuLV-reactive sequences, some contained MCF env sequences only and bthers contained both. (O'Neill, Repaske, Khan, Hoggan, Kozak) 9-7 Expression of MCF related mRNA in AKR mice . Expression of RNA transcripts containing MCF env - reactive sequences was monitored in a variety of AKR mouse tissues ranging in age from 5 weeks to 6 months using a MCF MuLV env - specific probe developed during the past year in our laboratory. MCF env RNA transcripts, 1.8 and 7.2 kb in size, were detected in the thymus of 5 week old animals. At 3 months, prior to the appearance of gross thymomas, full-length MCF MuLV genomes could be identified in preparations of polyadenylated thymus RNA. Using a different MuLV env specific probe, ecotropic MuLV mRNA transcripts (8.2 kb) could be detected in all tissues and increased in amount with the age in the AKR mice examined. These data suggest the recombi national event giving use to MCF viruses in the thymus are related to the appearance of the 1.8 and/or 7.2 kb transcripts and the recombination(s) are accomplished by 3 months of age. (Laigret, Khan, Rabson, Boulukos, Repaske) The LTR and 3' pol regions of leukemogenic and non-leukemogenic MCF MuLVs contain significant nucleotide differences . Infectious molecular cloned DNAs were obtained of leukemogenic MCF- 13 and non-leukemogenic MCF-lllA MuLVs. The nucleotide sequence of the LKTRs, 3' pol and env regions was Relafen 750 Mg determined. The results of comparative sequence analysis indicated: the LTR associated with MCF-13 is closely related to that present in xenotropic MuLVs, whereas the LTR sequence of MCF-lllA is identical except for 1 bp to the ecotropic proviral LTR; no significant sequence divergence was seen between MCF-13 and MCF-lllA in the env region; a 12 bp nucleotide stretch, characteristic of leukemogenic MCF MuLVs, was conserved in MCF-13 in Relafen 750mg the 3' pol^ region but was lacking in MCF-lllA. These results suggest that the leukemogenic potential of MCF-13 may reside in LTR and 3' pol sequences. (Theodore and Khan) A new transforming mouse retrovirus contains the ras oncogene . Two independent isolates of a transforming retrovirus was isolated from splenic tumors of NFS mice following inoculation with C25 LI MCF virus, originally identified by Dr. Janet Hartley, LIP, NIAID. A biologically active molecular clone of the transforming virus was extensively characterized. The 8.8 kb viral genome contained gag and pol genes indistinguishable from ecotropic MuLV based upon its restriction enzyme cleavage map. Approximately 1000 bp of late pol and env genes were replaced with non-viral sequences identified as ras by hybridization. Nucleotide sequencing of this region showed a 567 bp segment encoding p21 ras that was flanked on both 5' and 3' ends by presumptive mouse sequences. Oncogenicity of p21 coding sequences is based upon the arginine substitution at amino acid 12. The ras sequence was closely related to bas, H-ras , and Purchase Relafen Rasheed- ras , but more distantly related to T24 ras . (Frederickson, Rut! edge, O'Neill, Theodore, Martin and Hartley) The tRNA " class of endogenous retroviral sequences is present in the primate germline extending from humans Buy Relafen Online back through old world monkeys . A unique feature of the full-length class of human endogenous retroviral sequences is the presence of a primer binding site (pbs) complementary to tRNA " No other known infectious or endogenous mammalian retrovirus has such a pbs. The env segment of the full-length human endogenous retroviral family failed to 9-8 cross-hybridize or to have significant polynucleotide sequence homology with known infectious retroviruses. On the other hand, a labeled human retroviral env probe, hybridized quite well to chimpanzee, orangutan, gibbon, baboon and African green monkey chromosomal DMAs; it failed to react with owl monkey, squirrel monkey, gal ago and rodent DNA. An African green monkey (AGM) gene library was screened with a human endogenous retroviral env probe and representative regions of clones obtained were sequenced. Nucleotide sequence homology of the endogenous AGM and a human retroviral clone ranged from 80-88%; the primer binding sitegassociated with the AGM proviral DNA was also complementary to tRNA . This family of endogenous mammalian retrovirus thus entered the primate germline
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