scholarly journals Evidence for the horizontal acquisition of murine AKR virogenes by recent horizontal infection of the germ line

1982 ◽  
Vol 155 (4) ◽  
pp. 1120-1132 ◽  
Author(s):  
SJ O'Brien ◽  
JL Moore ◽  
MA Martin ◽  
JE Womack
Keyword(s):  
Genetic Distance ◽  
Dna Sequences ◽  
Germ Line ◽  
Leukemia Virus ◽  
Inbred Mouse ◽  
Distance Measures ◽  
Mouse Strains ◽  
Infection Model ◽  
Restriction Enzyme Digestion ◽  
Endogenous Virus

Several recent reports (8, 10, 11, 13) have established the biological and molecular genetic similarity between the endogenous AKV virus of strain AKR, and an N-ecotropic endogenous virus found in the genome of feral Japanese mice, Mus musculus molossinus. The similarities are so striking as to suggest a common origin of these viruses, which are present in some, but not all, inbred mouse strains. The virogenes of AKR mice may have been acquired by either: (a) common descent of AKR (and other AKV(+) strains) from a common ancestor of AKR and molossinus animals, or (b) horizontal germ line infection of the AKR strains by molossinus virus at 1;he strain's inception followed by fixation through inbreeding. The sexual descent model carries with it a prediction of relative consanguinity of the AKR strain and molossinus, whereas the horizontal infection model does not. We have examined the polymorphic allozyme (allelic isozyme) genotype of 51 nonvirus-related loci in 17 strains of mice including AKR, C58, BALB/c, Swiss, and molossinus. By comparing the composite allozyme genotype of different inbred and outbred mouse strains, the "genetic distance" statistic was derived. Genetic distance measures the degree of allelic substitution between populations and increases proportionately with the amount of time the populations have been reproductively isolated. The genetic distance computed between molossinus and AKR is large, nearly 5-10 times the distance between known related populations and strains (e.g., C57L vs. C57BL/6). Molossinus had a similarly large distance from AKV negative strains (Swiss, C57L) as it did from AKV- positive strains. Cellular DNA sequences that flank the integrated AKV provirus were analyzed by restriction enzyme digestion of liver DNA from molossinus, AKR, and additional inbred strains that express ecotropic murine leukemia virus. The integration flanks of three AKR provirus sequences, Akv-1, Akv-2, and a third uncharacterized sequence, were not evident in molossinus cell DNA, which contained at least six different proviral integration fragments. These data effectively exclude the interpretation of consanguinity of AKR and molossinus and support the notion of acquisition of the endogenous virus in AKR by horizontal infection of the molossinus virus.

scholarly journals Genetic Regulation of Long-Term Nonprogression in E-55+ Murine Leukemia Virus Infection in Mice

1999 ◽  
Vol 73 (11) ◽  
pp. 9232-9236
Author(s):  
Vily Panoutsakopoulou ◽  
Kathryn Hunter ◽  
Thomas G. Sieck ◽  
Elizabeth P. Blankenhorn ◽  
Kenneth J. Blank
Keyword(s):  
Bone Marrow ◽  
Murine Leukemia Virus ◽  
Genetic Locus ◽  
Leukemia Virus ◽  
Inbred Mouse ◽  
Major Histocompatibility Complex Gene ◽  
Mouse Strains ◽  
Term Survival ◽  
Murine Leukemia

ABSTRACT Certain inbred mouse strains display progression to lymphoma development after infection with E-55+ murine leukemia virus (E-55+ MuLV), while others demonstrate long-term nonprogression. This difference in disease progression occurs despite the fact that E-55+ MuLV causes persistent infection in both immunocompetent BALB/c–H-2k (BALB.K) progressor (P) and C57BL/10–H-2k (B10.BR) long-term nonprogressor (LTNP) mice. In contrast to immunocompetent mice, immunosuppressed mice from both P and LTNP strains develop lymphomas about 2 months after infection, indicating that the LTNP phenotype is determined by the immune response of the infected mouse. In this study, we used bone marrow chimeras to demonstrate that the LTNP phenotype is associated with the genotype of donor bone marrow and not the recipient microenvironment. In addition, we have mapped a genetic locus that may be responsible for the LTNP trait. Microsatellite-based linkage analysis demonstrated that a non-major histocompatibility complex gene on chromosome 15 regulates long-term survival and is located in the same region as the Rfv3 gene. Rfv3 is involved in recovery from Friend virus-induced leukemia and has been demonstrated to regulate neutralizing virus antibody titers. In our studies, however, both P and LTNP strains produce similar titers of neutralizing and cytotoxic anti-E-55+ MuLV. Therefore, while it is possible that Rfv3 influences the course of E-55+ MuLV infection, it is more likely that the LTNP phenotype in E-55+ MuLV-infected mice is regulated by a different, closely linked gene.

scholarly journals Molecular Markers for the agouti Coat Color Locus of the Mouse

Genetics ◽  
1987 ◽  
Vol 115 (4) ◽  
pp. 747-754
Author(s):  
Michael Lovett ◽  
Zai-yu Cheng ◽  
Estrella M Lamela ◽  
Tohru Yokoi ◽  
Charles J Epstein
Keyword(s):  
Molecular Markers ◽  
Dna Sequences ◽  
Coat Color ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Single Copy ◽  
Mouse Strains ◽  
Chromosome 2 ◽  
Agouti Locus ◽  
Lethal Yellow

ABSTRACT The agouti (a) coat color locus of the mouse acts within the microenvironment of the hair follicle to control the relative amount and distribution of yellow and black pigment in the coat hairs. Over 18 different mutations with complex dominance relationships have been described at this locus. The lethal yellow (Ay) mutation is the top dominant of this series and is uniquely associated with an endogenous provirus, Emv-15, in three highly inbred strains. However, we report here that it is unlikely that the provirus itself causes the Ay-associated alteration in coat color, since one strain of mice (YBR-Ay/a) lacks the provirus but still retains a yellow coat color. Using single-copy mouse DNA sequences from the regions flanking Emv-15 we have detected three patterns of restriction fragment length polymorphisms (RFLPs) within this region that can be used as molecular markers for different agouti locus alleles: a wild-type agouti (A) pattern, a pattern which generally cosegregates with the nonagouti (a) mutation, and a pattern which is specific to Emv-15. We have used these RFLPs and a panel of 28 recombinant inbred mouse strains to determine the genetic linkage of these sequences with the agouti locus and have found complete concordance between the two (95% confidence limit of 0.00 to 3.79 centimorgans). We have also physically mapped these sequences by in situ hybridization to band H1 of chromosome 2, thus directly confirming previous assignments of the location of the agouti locus.

Genetic divergence in mandible form in relation to molecular divergence in inbred mouse strains.

Genetics ◽  
1988 ◽  
Vol 120 (1) ◽  
pp. 239-253
Author(s):  
W R Atchley ◽  
S Newman ◽  
D E Cowley
Keyword(s):  
Genetic Distance ◽  
Genetic Divergence ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Morphological Data ◽  
Mouse Strains ◽  
Genealogical Relationship ◽  
Inbred Strains Of Mice ◽  
Molecular Divergence ◽  
Highly Correlated

Abstract Genetic divergence in the form of the mandible is examined in ten inbred strains of mice. Several univariate and multivariate genetic distance estimates are given for the morphological data and these estimates are compared to measures of genealogical and molecular divergence. Highly significant divergence occurs among the ten strains in all 11 mandible traits considered individually and simultaneously. Genealogical relationship among strains is highly correlated with genetic divergence in single locus molecular traits. However, the concordance between genealogical relationship and multivariate genetic divergence in morphology is much more complex. Whether there is a significant correlation between morphological divergence and genealogy depends upon the method of analysis and the particular genetic distance statistic being employed.

scholarly journals Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.

1995 ◽  
Vol 15 (10) ◽  
pp. 5434-5443 ◽  
Author(s):  
J J Moskow ◽  
F Bullrich ◽  
K Huebner ◽  
I O Daar ◽  
A M Buchberg
Keyword(s):  
Myeloid Leukemia ◽  
Leukemia Virus ◽  
Inbred Mouse ◽  
Homeobox Gene ◽  
Genetic Alterations ◽  
Tumor Formation ◽  
Mouse Strains ◽  
Control Mechanisms ◽  
Chromosome 11 ◽  
Altered Expression

Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation. The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus. Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias. Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript. A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified. The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins. Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice.

scholarly journals Induction of recessive lethal mutations in the T/t–H-2 region of the mouse genome by a point mutagen

1986 ◽  
Vol 47 (2) ◽  
pp. 135-142 ◽  
Author(s):  
Alexandra Shedlovsky ◽  
Jean-Louis Guenet ◽  
Lawrence L. Johnson ◽  
William F. Dove
Keyword(s):  
Recombinant Dna ◽  
Germ Line ◽  
Inbred Mouse ◽  
Chromosome 17 ◽  
Mouse Strains ◽  
Recessive Lethal ◽  
Lethal Mutations ◽  
Natural Variants ◽  
Breeding Schemes ◽  
Molecular Anatomy

SUMMARYThe T/t–H-2 region on mouse chromosome 17 is known from complex natural variants (‘t-haplotypes’) to contain numerous genes, including some affecting the immune system and the development of the embryo. Rapid progress in the isolation of recombinant DNA clones for this 50 megabasepair region is generating the material for its complete molecular anatomy. A crucial step in revealing the biological functions controlled by the region is to obtain mutants in which genes are inactivated individually. We have used a pair of inbred mouse strains and a series of classical breeding schemes that permit the detection of recessive lethal and detrimental mutations in the T/t–H-2 region.In this initial phase of our study, 280 gametes mutagenized in the male germ line by ethylnitrosourea (ENU) have yielded eleven independent pre-natal recessive lethal mutations. Four have been mapped against T mutations and have been shown to complement one another in all pairwise combinations.

scholarly journals Precise Identification of Endogenous Proviruses of NFS/N Mice Participating in Recombination with Moloney Ecotropic Murine Leukemia Virus (MuLV) To Generate Polytropic MuLVs

2005 ◽  
Vol 79 (8) ◽  
pp. 4664-4671 ◽  
Author(s):  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Marc Lavignon ◽  
Frank Malik ◽  
Leonard H. Evans
Keyword(s):  
Rna Secondary Structure ◽  
Frameshift Mutation ◽  
Leukemia Virus ◽  
Inbred Mouse ◽  
Surface Glycoprotein ◽  
Mouse Strains ◽  
Precise Identification ◽  
Maximum Stability ◽  
Leukemia Viruses ◽  
Murine Leukemia

ABSTRACT Polytropic murine leukemia viruses (MuLVs) are generated by recombination of ecotropic MuLVs with env genes of a family of endogenous proviruses in mice, resulting in viruses with an expanded host range and greater virulence. Inbred mouse strains contain numerous endogenous proviruses that are potential donors of the env gene sequences of polytropic MuLVs; however, the precise identification of those proviruses that participate in recombination has been elusive. Three different structural groups of proviruses in NFS/N mice have been described and different ecotropic MuLVs preferentially recombine with different groups of proviruses. In contrast to other ecotropic MuLVs such as Friend MuLV or Akv that recombine predominantly with a single group of proviruses, Moloney MuLV (M-MuLV) recombines with at least two distinct groups. In this study, we determined that only three endogenous proviruses, two of one group and one of another group, are major participants in recombination with M-MuLV. Furthermore, the distinction between the polytropic MuLVs generated by M-MuLV and other ecotropic MuLVs is the result of recombination with a single endogenous provirus. This provirus exhibits a frameshift mutation in the 3′ region of the surface glycoprotein-encoding sequences that is excluded in recombinants with M-MuLV. The sites of recombination between the env genes of M-MuLV and endogenous proviruses were confined to a short region exhibiting maximum homology between the ecotropic and polytropic env sequences and maximum stability of predicted RNA secondary structure. These observations suggest a possible mechanism for the specificity of recombination observed for different ecotropic MuLVs.

scholarly journals Suppression of endogenous murine leukemia virus by maternal resistance factor.

1983 ◽  
Vol 158 (2) ◽  
pp. 506-514 ◽  
Author(s):  
M Melamedoff ◽  
F Lilly ◽  
M L Duran-Reynals
Keyword(s):  
Murine Leukemia Virus ◽  
Infectious Virus ◽  
Leukemia Virus ◽  
Inbred Mouse ◽  
Resistance Factor ◽  
Mouse Strains ◽  
B Mice ◽  
Akr Mice ◽  
Old Females ◽  
Murine Leukemia

Females of the RF and SJL inbred mouse strains transmit to their progeny of both sexes a nonmendelian maternal resistance factor (MRF) able to suppress the expression of endogenous ecotropic murine leukemia virus (E-MuLV). This MRF is demonstrable in crosses with AKR mice by comparing E-MuLV expression in the spleens and thymuses of reciprocal F1 generations. DBA/2 and ST/b mice are MRF negative by these criteria. Neonatal inoculation of E-MuLV-containing spleen extracts gives rise to persistent expression of infectious virus in mice of the MRF- but not the MRF+ strains. However, inoculation of the virus in 30-d-old females of the MRF- strains no longer leads to a state of persistent infection; instead, these females become MRF+ and transmit protection against E-MuLV expression to their progeny by AKR and RF males. The MRF appears to be transmitted to the progeny mainly through the milk, since foster-nursing AKR neonates on RF (but not DBA/2) mothers greatly reduces E-MuLV expression in the progeny. These RF-fostered AKR mice also show a reduced and delayed lymphoma incidence, a finding consistent with the idea that maternally transmitted resistance to E-MuLV expression is the basis for the classic maternal resistance to lymphomagenesis seen in the progeny of RF mothers.

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