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 Transmission-Ratio Distortion Through F1 Females at Chromosome 11 Loci Linked to Om in the Mouse DDK Syndrome

Genetics ◽  
1996 ◽  
Vol 142 (4) ◽  
pp. 1299-1304
Author(s):  
F Pardo-Manuel de Villena ◽  
C Slamka ◽  
M Fonseca ◽  
A K Naumova ◽  
J Paquette ◽  
...  
Keyword(s):  
Genetic Model ◽  
Inbred Mouse ◽  
Transmission Ratio Distortion ◽  
Transmission Ratio ◽  
F1 Hybrids ◽  
Mouse Strains ◽  
Inbred Mouse Strains ◽  
Chromosome 11 ◽  
Ratio Distortion

Abstract We determined the genotypes of >200 offspring that are survivors of matings between female reciprocal F1 hybrids (between the DDK and C57BL/6J inbred mouse strains) and C57BL/6J males at markers linked to the Ovum mutant (Om) locus on chromosome 11. In contrast to the expectations of our previous genetic model to explain the “DDK syndrome,” the genotypes of these offspring do not reflect preferential survival of individuals that receive C57BL/6J alleles from the F1 females in the region of chromosome 11 to which the Om locus has been mapped. In fact, we observe significant transmission-ratio distortion in favor of DDK alleles in this region. These results are also in contrast to the expectations of Wakasugi's genetic model for the inheritance of Om, in which he proposed equal transmission of DDK and non-DDK alleles from F1 females. We propose that the results of these experiments may be explained by reduced expression of the maternal DDK Om allele or expression of the maternal DDK Om allele in only a portion of the ova of F1 females

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 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.

Ozone-induced acute lung injury: genetic analysis of F2 mice generated from A/J and C57BL/6J strains

1999 ◽  
Vol 277 (2) ◽  
pp. L372-L380 ◽  
Author(s):  
Daniel R. Prows ◽  
Mark J. Daly ◽  
Howard G. Shertzer ◽  
George D. Leikauf
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Genetic Analysis ◽  
Survival Time ◽  
Complex Disease ◽  
Major Gene ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Survival Times ◽  
Chromosome 11

Acute lung injury (or acute respiratory distress syndrome) is a devastating and often lethal condition. This complex disease (trait) may be associated with numerous candidate genes. To discern the major gene(s) controlling mortality from acute lung injury, two inbred mouse strains displaying contrasting survival times to 10 parts/million ozone were identified. A/J (A) mice were sensitive [6.6 ± 1 (SE) h] and C57BL/6J (B) were resistant (20.6 ± 1 h). The designation for these phenotypes was 13 h, a point that clearly separated their survival time distributions. Our prior segregation studies suggested that survival time to ozone-induced acute lung injury was a quantitative trait, and genetic analysis identified three linked loci [acute lung injury-1, -2, and -3 ( Ali1–3, respectively)]. In this report, acute lung injury in A or B mice was characterized histologically and by measuring lung wet-to-dry weight ratios at death. Ozone produced comparable effects in both strains. To further delineate genetic loci associated with reduced survival, a genomewide scan was performed with F2 mice generated from the A and B strains. The results strengthen and extend our initial findings and firmly establish that Ali1 on mouse chromosome 11 has significant linkage to this phenotype. Ali3 was suggestive of linkage, supporting previous recombinant inbred analysis, whereas Ali2 showed no linkage. Together, our findings support the fact that several genes, including Ali1 and Ali3, control susceptibility to death after acute lung injury. Identification of these loci should allow a more focused effort to determine the key events leading to mortality after oxidant-induced acute lung injury.

scholarly journals In silico QTL mapping of basal liver iron levels in inbred mouse strains

2011 ◽  
Vol 43 (3) ◽  
pp. 136-147 ◽  
Author(s):  
Stela McLachlan ◽  
Seung-Min Lee ◽  
Teresa M. Steele ◽  
Paula L. Hawthorne ◽  
Matthew A. Zapala ◽  
...  
Keyword(s):  
Iron Status ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Mouse Strains ◽  
Chromosome 11 ◽  
Liver Iron ◽  
Functional Studies ◽  
A Genome ◽  
Genotype Information ◽  
Diferric Transferrin

Both iron deficiency and iron excess are detrimental in many organisms, and previous studies in both mice and humans suggest that genetic variation may influence iron status in mammals. However, these genetic factors are not well defined. To address this issue, we measured basal liver iron levels in 18 inbred strains of mice of both sexes on a defined iron diet and found ∼4-fold variation in liver iron in males (lowest 153 μg/g, highest 661 μg/g) and ∼3-fold variation in females (lowest 222 μg/g, highest 658 μg/g). We carried out a genome-wide association mapping to identify haplotypes underlying differences in liver iron and three other related traits (copper and zinc liver levels, and plasma diferric transferrin levels) in a subset of 14 inbred strains for which genotype information was available. We identified two putative quantitative trait loci (QTL) that contain genes with a known role in iron metabolism: Eif2ak1 and Igf2r. We also identified four putative QTL that reside in previously identified iron-related QTL and 22 novel putative QTL. The most promising putative QTL include a 0.22 Mb region on Chromosome 7 and a 0.32 Mb region on Chromosome 11 that both contain only one candidate gene, Adam12 and Gria1, respectively. Identified putative QTL are good candidates for further refinement and subsequent functional studies.

Quantitative trait locus mapping of genes regulating pulmonary PKC activity and PKC-α content

2000 ◽  
Vol 279 (2) ◽  
pp. L326-L332 ◽  
Author(s):  
Lori D. Dwyer-Nield ◽  
Beverly Paigen ◽  
Stephanie E. Porter ◽  
Alvin M. Malkinson
Keyword(s):  
Quantitative Trait Locus ◽  
Likelihood Ratio ◽  
Quantitative Trait ◽  
Single Gene ◽  
Inbred Mouse ◽  
Likelihood Ratio Statistic ◽  
Mouse Strains ◽  
Chromosome 11 ◽  
Major Locus ◽  
Trait Locus

Strain A/J mice, which are predisposed to experimentally induced asthma and adenocarcinoma, have the lowest pulmonary protein kinase (PK) C activity and content among 22 inbred mouse strains. PKC in neonatal A/J mice is similar to that in other strains, so this difference reflects strain-dependent postnatal regulation. PKC activity is 60% higher in C57BL/6J (B6) than in A/J lungs, and the protein and mRNA concentrations of PKC-α, the major pulmonary PKC isozyme, are two- to threefold higher in B6 mice. These differences result from more than a single gene as assessed in F1, F2, and backcross progeny of B6 and A/J parents. Quantitative trait locus (QTL) analysis of 23 A×B and B×A recombinant inbred strains derived from B6 and A/J progenitors indicates a major locus regulating lung PKC-α content that maps near the Pkcα structural gene on chromosome 11 ( D11MIT333; likelihood ratio statistic = 12.5) and a major locus controlling PKC activity that maps on chromosome 3 ( D3MIT19; likelihood ratio statistic = 15.4). The chromosome 11 QTL responsible for low PKC-α content falls within QTLs for susceptibilities to lung tumorigenesis and ozone-induced toxicity.

scholarly journals Genetic differences in the behavioral organization of binge eating, conditioned food reward, and compulsive-like eating in C57BL/6J and DBA/2J strains

2017 ◽  
Author(s):  
Richard K. Babbs ◽  
Julia C. Kelliher ◽  
Julia L. Scotellaro ◽  
Kimberly P. Luttik ◽  
Megan K. Mulligan ◽  
...  
Keyword(s):  
Binge Eating ◽  
Food Reward ◽  
Drugs Of Abuse ◽  
Bitter Taste ◽  
Inbred Mouse ◽  
Genetic Differences ◽  
Mouse Strains ◽  
Chromosome 6 ◽  
Chromosome 11 ◽  
Narrow Sense Heritability

ABSTRACTBinge eating (BE) is a heritable symptom of eating disorders associated with anxiety, depression, malnutrition, and obesity. Genetic analysis of BE could facilitate therapeutic discovery. We used an intermittent, limited access BE paradigm involving sweetened palatable food (PF) to examine genetic differences in BE, conditioned food reward, and compulsive-like eating between C57BL/6J (B6J) and DBA/2J (D2J) inbred mouse strains. D2J mice showed a robust escalation in intake and conditioned place preference for the PF-paired side. D2J mice also showed a unique style of compulsive-like eating in the light/dark conflict test where they rapidly hoarded and consumed PF in the preferred unlit environment. BE and compulsive-like eating exhibited narrow-sense heritability estimates between 56 and 73 percent. To gain insight into the genetic basis, we phenotyped and genotyped a small cohort of 133 B6J × D2J-F2 mice at the peak location of three quantitative trait loci (QTL) previously identified in F2 mice for sweet taste (chromosome 4: 156 Mb), bitter taste (chromosome 6: 133 Mb) and behavioral sensitivity to drugs of abuse (chromosome 11: 50 Mb). The D2J allele on chromosome 6 was associated with greater PF intake on training days and greater compulsive-like PF intake, but only in males, suggesting that decreased bitter taste may increase BE in males. The D2J allele on chromosome 11 was associated with an increase in final PF intake and slope of escalation across days. Future studies employing larger crosses and genetic reference panels comprising B6J and D2J alleles will identify causal genes and neurobiological mechanisms.

scholarly journals Intima modifier locus 2 controls endothelial cell activation and vascular permeability

2014 ◽  
Vol 46 (17) ◽  
pp. 624-633 ◽  
Author(s):  
Elaine M. Smolock ◽  
Ryan M. Burke ◽  
Chenjing Wang ◽  
Tamlyn Thomas ◽  
Sri N. Batchu ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Cell Activation ◽  
Inbred Mouse ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Vascular Wall ◽  
Mouse Strains ◽  
Leukocyte Infiltration ◽  
Chromosome 11 ◽  
Endothelial Cell Activation

Carotid intima formation is a significant risk factor for cardiovascular disease. C3H/FeJ (C3H/F) and SJL/J (SJL) inbred mouse strains differ in susceptibility to immune and vascular traits. Using a congenic approach we demonstrated that the Intima modifier 2 ( Im2) locus on chromosome 11 regulates leukocyte infiltration. We sought to determine whether inflammation was due to changes in circulating immune cells or activation of vascular wall cells in genetically pure Im2 (C3H/F.SJL.11.1) mice. Complete blood counts showed no differences in circulating monocytes between C3H/F and C3H/F.SJL.11.1 compared with SJL mice. Aortic vascular cell adhesion molecule-1 (VCAM-1) total protein levels were dramatically increased in SJL and C3H/F.SJL.11.1 compared with C3H/F mice. Immunostaining of aortic endothelial cells (EC) showed a significant increase in VCAM-1 expression in SJL and C3H/F.SJL.11.1 compared with C3H/F under steady flow conditions. Immunostaining of EC membranes revealed a significant decrease in EC size in SJL and C3H/F.SJL.11.1 vs. C3H/F in regions of disturbed flow. Vascular permeability was significantly higher in C3H/F.SJL.11.1 compared with C3H/F. Our results indicate that Im2 regulation of leukocyte infiltration is mediated by EC inflammation and permeability. RNA sequencing and pathway analyses comparing genes in the Im2 locus to C3H/F provide insight into candidate genes that regulate vascular wall inflammation and permeability highlighting important genetic mechanisms that control vascular intima in response to injury.

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