title: RIII/Sa mice with a high incidence of mammary tumors express two exogenous strains and one potential endogenous strain of mouse mammary tumor virus.
abstract: The inbred mouse strain RIII has long been known for shedding large amounts of mouse mammary tumor virus (MMTV) particles in milk and for the development of hormone-dependent early mammary tumors at a very high incidence (>90%). We have established one RIII subline (RIII/Sa) that shows a pattern of virus expression and tumor incidence similar to that in RIII mice. In the present study, we analyzed the milk and mammary tumors of RIII/Sa mice for virus characterization by reverse transcriptase PCR (RT-PCR) cloning and sequencing of the open reading frame (ORF) of the MMTV long terminal repeats (LTRs). Our results show that these mice express a mixture of at least three different MMTV strains, two of which, designated here as RIII/Sa MMTV-1 and RIII/Sa MMTV-2, are exogenous. The third virus, RIII/Sa MMTV-3, appears to carry the signature of an endogenous provirus, Mtv-17. Similar studies done with the milk and mammary glands of another subline, RIIIS/J, revealed that they do not express MMTV in their milk. The RIII/Sa and RIIIS/J mice also exhibited differences in their endogenous proviral contents. Twelve spontaneously developed mammary tumors of RIII/Sa mice were examined for possible Wnt-1 and/or int-2/Fgf3 mutations that are usually found to occur in most mouse mammary tumors as a consequence of MMTV proviral integration. This work led to the isolation of one MMTV-Wnt-1 junction fragment and one MMTV-int-2/Fgf3 junction fragment from 2 of the 12 tumors. Further analyses showed that both junction fragments contained the RIII/Sa MMTV-2-specific LTR ORF, indicating that this virus was involved in the development of both tumors. Whether RIII/Sa MMTV-1 and/or RIII/Sa MMTV-3 plays any role in mammary tumor development in RIII/Sa mice remains to be established. Overall, the present study demonstrates, to our surprise, that (i) RIII/Sa mice express, unlike other native mouse strains, three strains of MMTVs; and (ii) the virions are completely different from the virus expressed by another subline of RIII mice, the BR6 mice.
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA. nsarkar@mail.mcg.edu
authors.forename: Nurul H
authors.initials: NH
authors.lastname: Sarkar
authors.forename: Tatyana
authors.initials: T
authors.lastname: Golovkina
authors.forename: Taher
authors.initials: T
authors.lastname: Uz-Zaman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005260:Female; D015994:Incidence; D008321:Mammary Glands, Animal / Q000821:virology*; D008325:Mammary Neoplasms, Experimental / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008892:Milk / Q000821:virology*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D012192:Retroviridae Infections / Q000453:epidemiology / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D020079:Terminal Repeat Sequences / Q000235:genetics; D014412:Tumor Virus Infections / Q000453:epidemiology / Q000821:virology*
chemical_list: D012367:RNA, Viral