Disease relevance of Mtv2

• Localization of a gene for expression of mouse mammary tumor virus antigens in the GR/Mtv-2- mouse strain [1].
• The GR/Mtv-2- mouse strain is congenic to the GR strain but lacks the Mtv-2 gene for high amounts of mouse mammary tumor virus (MMTV) virion particles in the milk and early mammary tumors [1].
• In this study we analyzed the involvement of these nonpathogenic endogenous proviruses in the mammary gland tumors caused by Mtv-2 [2].
• One of these, Mtv-2, is unique because it causes mammary carcinomas in virtually 100% of breeding GR females prior to 1 year of age [3].
• In GR mice, the expression of Mtv-2, an endogenous proviral MMTV, leads to 100% incidence of mammary ductal hyperplasias and tumors [4].

High impact information on Mtv2

• The gene was thereby not allelic to any of the previously described MMTV induction genes, Mtv-1 and Mtv-2, and is therefore called Mtv-3 [1].
• The locus was called "Mtv-4" and was only comparable with Mtv-2 of the GR mouse strain in its inducing capacity of mammary cancer [5].
• Identification of the Mtv-2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization [6].
• The WXG-2 line was constructed by making hybrids between the GR strain and a wild mouse line free of both endogenous and exogenous MMTV, backcrossing to the MMTV-free line, and fixing the Mtv-2 locus in a population with the desired genotype [3].
• In DDDfDDD-Mtv-2, DDD neonatally infected with Mtv-2-derived exogenous MMTV (MMTV-2), neither LN cells nor thymus weight increased [7].

Biological context of Mtv2

• In addition, the Mtv-2 deletion phenotype was age dependent [8].
• Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain [9].
• Specifically, we have examined tumors from primary foster-nursed (GRf) mice to determine if MMTV proviruses derived from Mtv-2 were scattered randomly throughout the genome or were clustered in the vicinity of the int-1 and int-2 loci, which are thought to be associated with mammary tumorigenesis [10].
• A single dominant gene on chromosome 18, Mtv-2, controls both the early appearance of mammary tumors and expression of mouse mammary tumor virus (MMTV) in the milk [11].
• To investigate the effects of the T-cell deprivation on viral mammary tumorigenesis, two double congenic mouse strains of the DDD genetic background, DDD/1-Mtv-2/Mtv-2, nu/nu and DDD/1-Mtv-2/Mtv-2, nu/+, were produced by the cross between DDD/1-Mtv-2/Mtv-2 (DDD-Mtv-2) and DDD/1-nu/nu mice, followed by repeated intercross breedings [12].

Anatomical context of Mtv2

• Thus, Mtv-2- and MMTV-2-induced V beta 14+ T cell deletion may reflect intrathymic and peripheral elimination, respectively [7].
• In DDD-Mtv-2/Mtv-2 (DDD-Mtv-2) congenics, T cells were 4- to 18-fold increased depending on ages but B cells doubled at the most [7].

Associations of Mtv2 with chemical compounds

• The Mtv-2-induced expansion of LN T cells was polyclonal and appeared indigenous to DDD mice [7].

Regulatory relationships of Mtv2

• These findings suggest a role for Mtv-17 in the mammary gland tumors induced by Mtv-2 in GR mice [2].

Other interactions of Mtv2

• Endogenous mouse mammary tumor virus Mtv-17 is involved in Mtv-2-induced tumorigenesis in GR mice [2].
• This transcript initiates at the same site in the MMTV LTR as already reported for Mtv-2 and Mtv-8 [13].
• The differential sensitivity of mammary tissues from GR and GR/Mtv-2-mouse strains to the actions of prolactin and tumor promoter is directly correlated to their different incidences of spontaneous tumor formation; it is not known if there is a causal relationship [14].

Analytical, diagnostic and therapeutic context of Mtv2

• The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk [9].
• Southern blot analysis of the liver DNA from the resulting congenic mice with EcoRI and MMTV-U3 prove revealed that two DNA fragments corresponding to Mtv-2 were specifically transferred from GR to congenic mice [11].

References