Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Genetic background”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed2005

High incidence, early onset of histiocytic sarcomas in mice with Hertwig's anemia.

OBJECTIVE: Histiocytic sarcoma (HS) is a rare, rapidly disseminated, usually lethal tumor in humans. Treatment specific for HS has not been developed primarily due to deficiencies of appropriate animal models with high incidence/early onset. Mice with Hertwig's anemia (an/an) provide a potential model. METHODS: Here, we compare HS susceptibility in an/an and unaffected control mice maintained on three genetic backgrounds. As a potential therapeutic measure, genetically marked bone marrow is transplanted between high and low susceptibility animals. RESULTS: HS is detected earlier and the overall incidence is 15-fold higher in WBB6F1(F1)-an/an than in F1-+/?, B6-an/an and -+/? mice. Neither WB-an/an nor their normal WB-+/? littermates present with HS. Liver myelopoiesis and aneuploidy coexist with HS but the former is also rampant (33.7% incidence) in HS-free +/? and an/an mice. Marrow transplantation experiments provide evidence that (1) myelopoiesis is associated with HS and (2) early-onset/high-incidence HS is blocked by using late-onset F1-+/+ mice, as either donor or recipient. CONCLUSIONS: Homozygosity for an on an F1 genetic background is essential for high-incidence/early-onset HS; myelopoiesis and HS coexist; and therapeutic transplantation may be feasible.

Animals↗
PubMed2002

Blepharospasm: recent advances.

Benign essential blepharospasm is a common focal dystonia characterized by involuntary eyelid closure. Its etiology, supported by animal models, appears to be multifactorial, representing the influence of a genetic background and an environmental trigger. The genetic background could be responsible for the reduced brain inhibition, identified with physiologic studies that would set up a permissive condition for increased brain plasticity. Reduced D2 receptors identified with PET might be an indicator of this reduced inhibition. The trigger could be repetitive use or local ocular disease. Although symptomatic therapy is available, better approaches are needed and will likely become available as the genetics and pathophysiology become well understood.

Animals↗
PubMed1998

Did the four human cancer cell lines DLD-1, HCT-15, HCT-8, and HRT-18 originate from one and the same patient?

Four human colon cancer cell lines, HCT-8, HRT-18, DLD-1, and HCT-15, with an epithelioid morphotype reproducibly formed alpha-catenin-deficient round cells. Using DNA fingerprinting, we found that these four cell lines have an identical genetic background. Our finding strongly suggests a genetic background for the reproducible loss of alpha-catenin and the ensuing acquisition of invasiveness in all four cell lines.

Colonic Neoplasms↗
PubMed1975

Influence of non-H-2 genotype on the response to H-2-linked mixed lymphocyte reaction stimulating (MLR-S) genes.

The intensity of the mixed lymphocyte reaction to H-2-linked mixed lymphocyte reaction stimulating genes is influenced by non-H-2 genotype. The same H-2 incompatibility results in a stronger mixed lymphocyte reaction when both partners have the C57BL/10ScSnPh genetic background than when they have the genetic background of the A/Ph strain. It is suggested that, as in man, the intensity of the mixed lymphocyte reaction to incompatibility at the MLR-S genes linked to the major histocompatibility complex is controlled by MLR-response genes not linked to MHS.

Animals↗
PubMed2000

Differences in the effect of ethanol on fertility and viability components among laboratory strains of Drosophila melanogaster.

We studied the effect of ethanol on several fitness components in six Drosophila melanogaster strains. Mating success, fecundity, egg-to-larva, egg-to-pupa and egg-to-adult survival and the number of emerging adults were estimated in a single series of experiments. The strains either had different combinations of genetic background and Adh genotypes with identical OdhF genotype or different Adh-Odh two-locus genotypes with similar genetic background. Ethanol had the greatest effect on mating success and fecundity, while its influence was lower on survival. When the experimental conditions were contrasted to the natural environment of the flies the most significant results were the ones related to fecundity and larval survival. Ethanol had the highest selective effect on fecundity. The genetic factors contributed substantially to the variation in the fertility and viability components. The Adh locus hardly influenced mating success while it had a sizable effect on fecundity and on all survival components. The influence of Adh on fecundity greatly depended on the other genetic factors. Genetic background had the largest influence on the different survival components. The influence of the Odh locus was mostly observed through the Adh-Odh interaction.

Alleles↗
PubMed2006

Genetic modifiers of the phenotype of mice deficient in mitochondrial superoxide dismutase.

Sod2-/- mice, which are deficient in the mitochondrial form of superoxide dismutase (MnSOD), have a short survival time that is strongly affected by genetic background. This suggests the existence of genetic modifiers that are capable of modulating the degree of mitochondrial oxidative damage caused by the MnSOD deficiency, thereby altering longevity. To identify these modifier(s), we generated recombinant congenic mice with quantitative trait loci (QTL) containing the putative genetic modifiers on the short-lived C57BL/6J genetic background. MnSOD deficient C57BL/6J mice with a QTL from the distal region of chromosome 13 from DBA/2J were able to survive for as long as those generated on the long-lived DBA/2J background. Within this region, the gene encoding nicotinamide nucleotide transhydrogenase (Nnt) was found to be defective in C57BL/6J mice, and no mature NNT protein could be detected. The forward reaction of NNT, a nuclear-encoded mitochondrial inner membrane protein, couples the generation of NADPH to proton transport and provides NADPH for the regeneration of two important antioxidant compounds, glutathione and thioredoxin, in the mitochondria. This action of NNT could explain its putative protective role in MnSOD-deficient mice.

Alleles↗
PubMed2006

Genetic basis of murine responses to hyperoxia-induced lung injury.

To evaluate the effect of genetic background on oxygen (O2) toxicity, nine genetically diverse mouse strains (129/SvIm, A/J, BALB/cJ, BTBR+(T)/tf/tf, CAST/Ei, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ) were exposed to more than 99% O2 for 72 h. Immediately following the hyperoxic challenge, the mouse strains demonstrated distinct pathophysiologic responses. The BALB/cJ and CAST/Ei strains, which were the only strains to demonstrate mortality from the hyperoxic challenges, were also the only strains to display significant neutrophil infiltration into their lower respiratory tract. In addition, the O2-challenged BALB/cJ and CAST/Ei mice were among six strains (A/J, BALB/cJ, CAST/Ei, BTBR+(T)/tf/tf, DBA/2J, and C3H/HeJ) that had significantly increased interleukin 6 concentrations in the whole lung lavage fluid and were among all but one strain that had large increases in lung permeability compared with air-exposed controls. In contrast, the DBA/2J strain was the only strain not to have any significant alterations in lung permeability following hyperoxic challenge. The expression of the extracellular matrix proteins, including collagens I, III, and IV, fibronectin I, and tenascin C, also varied markedly among the mouse strains, as did the activities of total superoxide dismutase (SOD) and manganese-SOD (Mn-SOD or SOD2). These data suggest that the response to O2 depends, in part, on the genetic background and that some of the strains analyzed can be used to identify specific loci and genes underlying the response to O2.

Animals↗
PubMed2001

Neurobiological effects of a null mutation depend on genetic context: comparison between two hotfoot alleles of the delta-2 ionotropic glutamate receptor.

Hotfoot is a mutant mouse with an ataxic phenotype which has been shown to be due to a mutation in the Grid2 gene. In this paper, we compare molecular, morphological, electrophysiological and behavioral features of two Grid2 alleles: Grid2(ho-4J) and Grid2(ho-Nancy). We first show that these two mutations are deletions in the open reading frame of the gene and that no GRID2 protein is detectable in extracts of mutant cerebella, suggesting that the two alleles are null-like mutations. Morphological and electrophysiological analyses reveal no obvious differences between the two strains: both strains showed the naked Purkinje dendritic spines and mismatch between the length of the presynaptic active zone and postsynaptic differentiation characteristic of the hotfoot mutation; and the same low level (20%) of multiple climbing fiber innervation of Purkinje cells was found in both strains. Only differences in motor behavior were found between the two strains. The Grid2(ho-4J) mouse shows more severe ataxia that the Grid2(ho-Nancy) mouse and, although both strains show a clear capacity to improve their performance of a motor task with training, the Grid2(ho-4J) performance remains very poor whereas Grid2(ho-Nancy) mice approach control levels. The only difference between the two strains is their genetic background. Our results show that the genetic background must be taken into account when analyzing sensorimotor performances of mutant mice.

Afferent Pathways↗
PubMed2005

Protection from lethal endotoxic shock after testosterone depletion is linked to chromosome X.

Men are considered more susceptible to sepsis after severe injury than are women, which has been attributed to a suppressing effect of male sex steroids on the inflammatory response. Moreover, the effect of sex steroids on the inflammatory process depends on the genetic background. The present study examined the genetic contribution to survival after endotoxic shock in mice depleted of testosterone by surgical castration. Six-week-old male mice, from strains A/J, AKR/J, C57BL/6J (B6), BALBc/J, DBA/2J, and C3H/HeN, were castrated (CX) or nonoperated (NoOp). Two weeks after surgery, mice were injected intraperitoneally with Escherichia coli lipopolysaccharide (15 mg/kg) and the frequency of mortality was monitored. CX A/J mice showed a significantly higher survival rate than NoOp mice, but this protective effect was not observed in the other strains. Administration of 5-alpha-dihydrotestosterone to CX A/J mice reverted the protection by CX. The protective effect of CX was also observed in crosses of female A/J and male B6 (AXB), but not female B6 and male A/J (BXA), suggesting that protection is linked to the A/J X chromosome. This possibility was corroborated by using consomic mice containing A/J chromosome X and the remaining chromosomes from B6. These results suggest that testosterone is a negative factor in the recovery from endotoxic shock, depending on the genetic background.

Animals↗
PubMed2001

HZE particle radiation induces tissue-specific and p53-dependent mutagenesis in transgenic animals.

Transgenic animals, with the integrated target gene, provide a unique approach for measuring and characterizing mutations in any tissue of the animal. We are using the plasmid-based lacZ transgenic mice with different p53 genetic background to examine radiation-induced genetic damage resulting from exposure to heavy particle radiation. We measured lacZ mutation frequencies (MF) in the brain and spleen tissues at various times after exposing animals to an acute dose of 1 Gy of 1GeV/amu iron particles. MF in the spleen of p53+/+ animals increased up to 2.6-fold above spontaneous levels at 8 weeks post irradiation. In contrast, brain MF from the same animals increased 1.7-fold above controls in the same period. In the p53-/- animals, brain MF increased to 2.2-fold above spontaneous levels at 1 week after treatment, but returned to control levels thereafter. Radiation also induced alterations in the spectrum of mutants in both tissues, accompanied by changes in the frequency of mutants with deletions extending past the transgene into mouse genomic DNA. Our results indicate that the accumulation of transgene MF after radiation exposure is dependant on the tissue examined as well as the p53 genetic background of the animals.

Animals↗
PubMed2006

Low-temperature tolerance and genetic potential in wheat (Triticum aestivum L.): response to photoperiod, vernalization, and plant development.

It is frequently observed that winter habit types are more low-temperature (LT) tolerant than spring habit types. This raises the question of whether this is due to pleiotropic effects of the vernalization loci or to the linkage of LT-tolerance genes to these vernalization loci. Reciprocal near-isogenic lines (NILs) for alleles at the Vrn-A1 locus, Vrn-A1 and vrn-A1, determining spring and winter habit respectively, in two diverse genetic backgrounds of wheat (Triticum aestivum L.) were used to separate the effects of vernalization, photoperiod, and development on identical, or near identical, genetic backgrounds. The vrn-A1 allele in the winter lines allowed full expression of genotype dependent LT tolerance potential. The winter allele (vrn-A1) in a very cold tolerant genetic background resulted in 11 degrees C, or a 2.4-fold, greater LT tolerance compared to the spring allele. Similarly, the delay in development caused by short-day (SD) versus long-day (LD) photoperiod in the identical spring habit NIL resulted in an 8.5 degrees C or 2.1-fold, increase in LT tolerance. The duration of time in early developmental stages was shown to underlie full expression of genetic LT-tolerance potential. Therefore, pleiotropic effects of the vernalization loci can explain the association of LT tolerance and winter habit irrespective of either the proposed closely linked Fr-A1 or the more distant Fr-A2 LT-tolerance QTLs. Plant development progressively reduced LT-acclimation ability, particularly after the main shoot meristem had advanced to the double ridge reproductive growth stage. The Vrn-1 genes, or other members of the flowering induction pathway, are discussed as possible candidates for involvement in LT-tolerance repression.

Acclimatization↗
PubMed2006

Opposite role of pro-inflammatory alleles in acute myocardial infarction and longevity: results of studies performed in a Sicilian population.

The major trait characterizing offspring in centenarians is a reduction in the prevalence of cardiovascular disease. Because a pro-inflammatory genotype seems to contribute significantly to the risk of coronary heart disease, alleles associated with disease susceptibility would not be included in the genetic background favoring longevity, as suggested by our previous studies on inflammatory cytokines. To confirm whether genotypes of inflammatory molecules play an opposite role in atherosclerosis and longevity, we are studying the role of other proinflammatory alleles, such as pyrin and CCR5, in acute myocardial infarction and longevity. The results support the hypothesis that the genetic background favoring cardiovascular diseases is detrimental to longevity. In addition, they suggest that the centenarian genetic background may be useful for investigating genetic key components of age-associated diseases that are characterized by a multifactorial etiology.

Acute Disease↗
PubMed2001

Epistasis, complex traits, and mapping genes.

Using a three-locus model wherein two loci regulate a third, candidate locus, I examine physiological epistasis from the 'gene's eye view' of the regulated locus. I show that, depending upon genetic background at the regulatory loci, an allele at the candidate locus can be dominant, additive, recessive, neutral, over-dominant, or under-dominant in its effects on fitness. This kind of variation in allelic effect caused by variation in genetic background from population to population, from time to time in the same population, or sample to sample makes finding and mapping the genes underlying a complex phenotype difficult. The rate of evolution of such genes can also be slowed, especially in genetically subdivided metapopulations with migration. Nevertheless, understanding how variation in genetic background causes variation in allelic effects permits the genetic architecture of such complex traits to be dissected into the interacting component genes. While some backgrounds diminish allelic effects and make finding and mapping genes difficult, other backgrounds enhance allelic effects and facilitate gene mapping.

Alleles↗
PubMed2005

Sexual dimorphisms in the effect of low-level p25 expression on synaptic plasticity and memory.

p25, a degradation product of p35, has been reported to accumulate in the forebrain of patients with Alzheimer's disease. p25 as well as p35 are activators of cyclin-dependent kinase 5 (Cdk5) although p25/Cdk5 and p35/Cdk5 complexes have distinct properties. Several mouse models with high levels of p25 expression exhibit signs of neurodegeneration. On the contrary, we have shown that low levels of p25 expression do not cause neurodegeneration and are even beneficial for particular types of learning and memory [Angelo et al., (2003) Eur J. Neurosci., 18, 423-431]. Here, we have studied the influence of low-level p25 expression in hippocampal synaptic plasticity and in learning and memory for each sex separately in two different genetic backgrounds (129B6F1 and C57BL/6). Surprisingly, we found that low-level p25 expression had different consequences in male and female mutants. In the two genetic backgrounds LTP induced by a strong stimulation of the Schaffer's collaterals (four trains, 1-s duration, 5-min interval) was severely impaired in male, but not in female, p25 mutants. Furthermore, in the two genetic backgrounds spatial learning in the Morris water maze was faster in female p25 mutants than in male transgenic mice. These results suggest that, in women, the production of p25 in Alzheimer's disease could be a compensation for some early learning and memory deficits.

Animals↗
PubMed1999

Impaired extrapyramidal function caused by the targeted disruption of retinoid X receptor RXRgamma1 isoform.

BACKGROUND: Retinoid X receptors RXRalpha, beta and gamma exert multiple functions in the genetic regulation of mammalian signalling systems by forming heterodimeric complexes with several nuclear ligand receptors. In contrast to the widespread expression of RXRalpha and RXRbeta, the expression of RXRgamma is restricted to particular tissues in which RXRgamma1 is the major isoform expressed in the mouse corpus striatum. RESULTS: To investigate the function of this particular isoform RXRgamma1, we generated RXRgamma1 gene-knockout mice by homologous recombination in ES cells. Both heterozygous and homozygous mice showed severe runting after birth, which often resulted in the early death of mice of the 129/C57BL-6 genetic background. Independent of genetic background, however, the expression of choline acetyltransferase (ChAT) in the cholinergic interneurones in the striatum (caudal putamen) was markedly reduced in the RXRgamma1 gene-null mice. Furthermore, the mutant exhibited an altered response to the administration of dopamine receptor antagonists, haloperidol and chlorpromazine, which normally induce catalepsy in mice. CONCLUSIONS: These results strongly suggest that RXRgamma1 plays an important role in either the development or activation of cholinergic neurones in nigrostriatal extrapyramidal pathways.

Animals↗
PubMed2005

Influence of nociception and stress-induced antinociception on genetic variation in isoflurane anesthetic potency among mouse strains.

BACKGROUND: Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensitivity to the noxious stimuli used to assess MAC has virtually never been studied. The authors assessed room air nociceptive sensitivity and isoflurane MAC in multiple mouse strains. Isoflurane requirement for loss of righting response (MACLORR) was also measured. METHODS: One outbred and 10 inbred mouse strains were tested for latency to respond (in room air) to a tail clip (either 500 g or 2,000 g). Naive mice of the same 11 strains were tested for isoflurane MAC and MACLORR. To assess the role of opioid-mediated stress-induced antinociception, mice were also tested for nociceptive sensitivity after injection of naloxone (10 mg/kg) or saline. RESULTS: Robust strain differences were observed for all measures. The authors found that tail-clip latency (using a 500-g or 2,000-g clip, respectively) correlated significantly with MAC (r = -0.76 and -0.58, respectively) but not MACLORR (r = -0.10 and -0.26). Naloxone produced strain-dependent reductions in open air tail-clip latencies, and these reductions were also strongly correlated with MAC (r = -0.67 and -0.71). CONCLUSIONS: The authors suggest that genetic variability in isoflurane MAC (but not MACLORR) may reflect genetic variability in the underlying sensitivity to the noxious stimulus being used to measure MAC. This variable sensitivity to nociception in the awake state is at least partially mediated by endogenous antinociceptive mechanisms activated by the tail-clip stimulus itself.

Anesthetics, Inhalation↗
PubMed2006

Comparison of different foreground and background selection methods in marker-assisted introgression.

Three different methods for foreground selection and four different methods for background selection were compared in terms of the efficiency of marker-assisted introgression of a QTL allele from a donor line into a recipient line and also in terms of the recovery of the recipient genetic background. The results showed that for the introgression of a donor QTL allele, a direct selection on the QTL itself (when the QTL genotype can be directly identified) would ensure that the allele is successfully introgressed and rapidly fixed. However, when a direct selection on the QTL is not feasible, an indirect selection using two closely linked flanking markers can be used, which also shows similar results. For the recovery of the recipient genetic background, if the goal is to recover the whole genetic background of the recipient, genomic similarity selection or marker index selection would be the best choice: Only three generations of backcrosses were required to recover over 98% of the recipient genome. Whereas if the goal is to recover certain background traits of the recipient, MBLUP selection would give the best results, which achieved not only over 99% recovery of the recipient QTL alleles for the background traits after three generations of backcrosses, but also showed the best genetic improvement of these traits.

Breeding↗
PubMed1983

The influence of the H-2 complex on responses to infection by Schistosoma mansoni in mice.

In order to determine whether a given H-2 haplotype has similar effects on responses to schistosomiasis mansoni on different genetic backgrounds, mice of 2 pairs of congenic strains (H-2b and H-2k on BALB/c and C57BL/10 backgrounds) were infected. Worm burdens, mortality, splenomegaly, tissue and faecal egg counts, and antibody titres to worm and egg antigens were measured. The genetic background had a major effect on the genesis of splenomegaly, on the deposition of eggs in the spleen, the maximum faecal egg count, the antibody titre to egg and worm antigens and the rate of generation of antibody response. The H-2 haplotype was shown to consistently influence the maximum faecal egg count and the antibody titres. Worm burden was not influenced by genetic differences between strains and mortality differences were not significant. The data presented here indicate that the effect of the major histocompatibility complex on responses to infection is greatly influenced by the genetic background on which it is expressed.

Animals↗