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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.

journal_name

J Virol

journal_title

Journal of virology

authors

Sarkar NH,Golovkina T,Uz-Zaman T

doi

10.1128/jvi.78.2.1055-1062.2004

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

1055-62

issue

eissn

0022-538X

issn

1098-5514

journal_volume

pub_type

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RIII/Sa mice with a high incidence of mammary tumors express two exogenous strains and one potential endogenous strain of mouse mammary tumor virus.