Sequences within the gag gene of mouse mammary tumor virus needed for mammary gland cell transformation.
Previously, we identified a group of replication-competent exogenous mouse mammary tumor viruses that failed to induce mammary tumors in susceptible mice. Sequence comparison of tumorigenic and tumor-attenuated virus variants has linked the ability of virus to cause high-frequency mammary tumors to the gag gene. To determine the specific sequences within the gag gene that contribute to tumor induction, we constructed five distinct chimeric viruses that have various amino acid coding sequences of gag derived from a tumor-attenuated virus replaced by those of highly tumorigenic virus and tested these viruses for tumorigenic capacities in virus-susceptible C3H/HeN mice. Comparing the tumorigenic potentials of these viruses has allowed us to map the region responsible for tumorigenesis to a 253-amino-acid region within the CA and NC regions of the Gag protein. Unlike C3H/HeN mice, BALB/cJ mice develop tumors when infected with all viral variants, irrespective of the gag gene sequences. Using genetic crosses between BALB/cJ and C3H/HeN mice, we were able to determine that the mechanism that confers susceptibility to Gag-independent mammary tumors in BALB/cJ mice is inherited as a dominant trait and is controlled by a single gene, called mammary tumor susceptibility (mts), that maps to chromosome 14.
Swanson
Ingrid
I
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Jude
Brooke A
BA
Zhang
Annie R
AR
Pucker
Andrew
A
Smith
Zachary E
ZE
Golovkina
Tatyana V
TV
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic; D002874:Chromosome Mapping; D002875:Chromosomes; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003433:Crosses, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D015750:Genes, gag; D005818:Genetic Engineering; D006239:Haplotypes; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000821:virology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis