A New Mutation With Asymmetrical Expression in the Mouse

Garber, E. D.; Hauth, Franziskus

doi:10.1093/oxfordjournals.jhered.a106105

Cited by 43 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the higher degree of binding in the two-hybrid assay between L9 and MMTV(C3H) Gag compared to MMT-V(HP/Mtv1), we tested whether L9 overexpression would change the localization of Gag derived from Mtv1. In fact, L9 overexpression also induced localization of a subpopulation of Mtv1 Gag to nucleoli (data not shown), indicating that the difference in binding affinity observed in the quantitative yeast two-hybrid assay was not apparent in NMuMG cells, which are derived from Namru mice (37)(38)(39). It is possible that Namru mice, like BALB/cJ mice, do not exhibit differences in the rates of tumor formation with variants of MMTV tested by Swanson et al (34) (Fig.…”

Section: Resultsmentioning

confidence: 79%

Nucleolar Trafficking of the Mouse Mammary Tumor Virus Gag Protein Induced by Interaction with Ribosomal Protein L9

Beyer

Bann

Rice

et al. 2013

J Virol

View full text Add to dashboard Cite

fThe mouse mammary tumor virus (MMTV) Gag protein directs the assembly in the cytoplasm of immature viral capsids, which subsequently bud from the plasma membranes of infected cells. MMTV Gag localizes to discrete cytoplasmic foci in mouse mammary epithelial cells, consistent with the formation of cytosolic capsids. Unexpectedly, we also observed an accumulation of Gag in the nucleoli of infected cells derived from mammary gland tumors. To detect Gag-interacting proteins that might influence its subcellular localization, a yeast two-hybrid screen was performed. Ribosomal protein L9 (RPL9 or L9), an essential component of the large ribosomal subunit and a putative tumor suppressor, was identified as a Gag binding partner. Overexpression of L9 in cells expressing the MMTV(C3H) provirus resulted in specific, robust accumulation of Gag in nucleoli. Förster resonance energy transfer (FRET) and coimmunoprecipitation analyses demonstrated that Gag and L9 interact within the nucleolus, and the CA domain was the major site of interaction. In addition, the isolated NC domain of Gag localized to the nucleolus, suggesting that it contains a nucleolar localization signal (NoLS). To determine whether L9 plays a role in virus assembly, small interfering RNA (siRNA)-mediated knockdown was performed. Although Gag expression was not reduced with L9 knockdown, virus production was significantly impaired. Thus, our data support the hypothesis that efficient MMTV particle assembly is dependent upon the interaction of Gag and L9 in the nucleoli of infected cells. Since its discovery as a milk-transmitted agent in the 1930s, the oncogenic retrovirus mouse mammary tumor virus (MMTV) has served as an important model in breast cancer research and immunology (1). However, little is known about the molecular mechanisms that govern MMTV assembly. The 9-kb MMTV RNA genome consists of the common retroviral elements gag, pro, pol, and env, as well as dut (dUTPase) (2), sag (superantigen) (3), and rem (regulator of export of MMTV mRNA) (4, 5). Like all retroviruses, MMTV uses full-length viral RNA to transcribe the viral structural proteins Gag, Gag-Pro, and Gag-Pro-Pol. The Gag protein directs assembly of complete, immature viral capsids in the cytoplasm, which are subsequently transported to the plasma membrane for release by budding.Unlike acutely transforming retroviruses like Rous sarcoma virus (RSV), MMTV does not carry an oncogene and instead induces tumors primarily by integrating near cellular oncogenes and disrupting their regulation. In addition, the MMTV Gag and Env proteins also promote tumorigenesis independently of the proviral integration site (6, 7). Moreover, differences in pathogenesis between the highly tumorigenic MMTV(C3H) strain and the tumor-attenuated MMTV hybrid provirus (HP) strain map to the CA and NC regions of the Gag protein (6), which led us to hypothesize that the Gag proteins from the C3H and HP strains might differentially interact with cellular proteins to promote malignant transformation.The eukaryotic ribos...

show abstract

Section: Resultsmentioning

confidence: 79%

Nucleolar Trafficking of the Mouse Mammary Tumor Virus Gag Protein Induced by Interaction with Ribosomal Protein L9

Beyer

Bann

Rice

et al. 2013

J Virol

View full text Add to dashboard Cite

show abstract

“…Formalin-killed spherule vaccines from C. immitis strain Silveira were prepared and purified as described previously (14). A total dose of 2.0 to 2.4 mg was given intramuscularly in 3 or 4 weekly injections (0.1 ml) to female albino mice of the Namru strain (6), beginning at 5 to 7 weeks of age (18 to 21 g). In one case, pulverized spherules (Savage, Ph.D. Thesis, Univ.…”

Section: Methodsmentioning

confidence: 99%

Delayed Dermal Hypersensitivity in Mice to Spherule and Mycelial Extracts ofCoccidioides immitis

1966

View full text Add to dashboard Cite

, D. C. SAVAGE, AND LEIGHTON N. L. KONG. Delayed dermal hypersensitivity in mice to spherule and mycelial extracts of Coccidioides immitis. J. Bacteriol. 91:876-883. 1966.-A delayed hypersensitivity reaction to spherule and mycelial extracts of Coccidioides immitis was elicited in the footpads of mice vaccinated with killed spherules. Emulsification of the spherules with Freund's adjuvants was unnecessary, but a high concentration of antigen was required to elicit the reaction. Injection of the extracts produced, initially, a swelling which subsided within 4 hr, and then induration, which began at 6 to 8 hr and reached a maximum at 24 hr. The time course of the reaction corresponded to that of the tuberculin reaction in BCG-vaccinated mice. The histological response to coccidioidal extracts was characterized by the early infiltration of both polymorphonuclear and mononuclear cells, and the subsequent predominance of mononuclear cells at 24 to 48 hr. By 72 hr, the mononuclear cells comprised >90% of the cellular infiltrate. Animals infected intranasally with arthrospores (1 to 5 LD15) reacted negatively before and during the crisis period; thereafter (by 28 to 31 days after infection), up to 50% of the survivors showed a delayed reaction.

show abstract

“…Albino female mice (Namru strain; Garber & Hauth, 1950) were given the first of 3 or 4 injections of vaccine (0.1 or 0.2 ml.) at 6 to 9 weeks of age (18 to 25 g.) either intramuscularly (i.m.)…”

Section: Vaccination and Challengementioning

confidence: 99%

Immunogenic properties of nondisrupted and disrupted spherules ofCoccidioides immitisin mice

1963

View full text Add to dashboard Cite

The immunogenicity for mice of the spherule-endospore phase of Coccidioides irnmitis was investigated in respect of the duration of immune response and the stability, locus, and specificity of the antigens. Formalinized vaccine retained potency during 20 months' storage at 4°C in the presence of formalin or after treatment with chloroform. Induced immunity did not decline during a 97-day interval between vaccination and challenge and was effective against lethal challenge with an heterologous strain of C. immitis. Nonspecific resistance to Cryptococcus neoformans or Pseudomonas (Malleomyces) pseudomallei was not induced by vaccination.Immunogenicity resided primarily, but not exclusively, in the wall structure of disrupted spherules; some activity was demonstrable in the s~luble protoplasmic moiety by the use of an adjuvant. A procedure for disrupting the spherules and isolating distinguishable wall fragments is described.

show abstract

A New Mutation With Asymmetrical Expression in the Mouse

Cited by 43 publications

References 0 publications

Nucleolar Trafficking of the Mouse Mammary Tumor Virus Gag Protein Induced by Interaction with Ribosomal Protein L9

Nucleolar Trafficking of the Mouse Mammary Tumor Virus Gag Protein Induced by Interaction with Ribosomal Protein L9

Delayed Dermal Hypersensitivity in Mice to Spherule and Mycelial Extracts ofCoccidioides immitis

Immunogenic properties of nondisrupted and disrupted spherules ofCoccidioides immitisin mice

Contact Info

Product

Resources

About