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 595 records · Page 33Linked to original sources
PubMed2003

Tularemia in BALB/c and C57BL/6 mice vaccinated with Francisella tularensis LVS and challenged intradermally, or by aerosol with virulent isolates of the pathogen: protection varies depending on pathogen virulence, route of exposure, and host genetic background.

In order to begin understanding the immunological basis for immunity to tularemia, and to establish a baseline for judging the efficacy of potential novel vaccines, the present study examined the ability of the live vaccine strain of Francisella tularensis (F. tularensis) LVS, to elicit immunity in mice against subsequent systemic and aerosol challenge with highly virulent strains of the pathogen. The results show, that infection with LVS protects BALB/c mice against systemic challenge with virulent Types A and B F. tularensis. In contrast, C57BL/6 mice vaccinated with LVS were only rendered immune to systemic challenge with Type B F. tularensis. Neither mouse strain immunized with LVS was able to resist aerosol challenge with Type A F. tularensis, and only immunized BALB/c mice withstood exposure to aerosols of Type B F. tularensis.

Aerosols↗
PubMed2002

The pathogenesis of inflammatory muscle diseases: on the cutting edge among the environment, the genetic background, the immune response and the dysregulation of apoptosis.

Inflammatory muscle diseases (IMD), including dermatomyositis (DM) and polymyositis (PM), affect skeletal muscle, leading to profound tissue modification. The etiology of IMD is unknown, but multiple steps of the disease pathogenesis have been identified. The main alterations involve the immune response. Cellular infiltrates found in the muscle provide strong evidence for the involvement of a preferential immune mechanism of muscle damage. The pathologic differences found between PM and DM indicate a different role played by cell-mediated and humoral immune alterations. It is well accepted that in the pathogenetic pathway both host genes and environmental factors are involved. Apoptosis, or programmed cell death, is a complex process that plays a key role in many physiological events. It regulates the turnover of immune cells and is one of the mechanisms involved in ensuring a competent, non-autoreactive repertoire of lymphocytes. Apoptosis as a mechanism of muscle fibre death has been described in several neuromuscular disorders and muscular dystrophies, and evidence of a lack of apoptosis in IMD suggests a failure of apoptotic clearance of inflammatory cells playing a role in the maintenance of chronic cytotoxic muscle fibre damage. Most likely, the failure of apoptosis seems to be the main hallmark of the pathogenesis of IMD.

Apoptosis↗
PubMed2004

Faecal shedding and intestinal colonization of Salmonella enterica in in-bred chickens: the effect of host-genetic background.

Considerable and reproducible differences were observed in the amount and duration of faecal excretion when in-bred lines of chickens were infected orally with S. enterica serovar Typhimurium at 6 weeks of age after being given a gut flora preparation when newly hatched. Similar but less pronounced results were observed with S. Enteritidis or S. Infantis. Differences in the viable numbers of the inoculated bacteria in caecal contents were detectable within 24 h of inoculation. No major differences were seen in Salmonella-specific serum IgA or IgG titres. Small differences were seen in the numbers of circulating heterophilic cells. Caecal contents taken from the more resistant lines immediately prior to challenge appeared to be no more inhibitory for Salmonella in vivo than contents taken from susceptible lines. The more resistant lines showed a slightly higher rate of intestinal flow, as indicated by the rate of production of faecal droppings, although there was no difference in the rate of emptying of the caeca. In an F1 generation resistance was dominant and not sex-linked. There was no MHC linkage or any association with SAL1, the gene implicated in resistance to systemic salmonellosis in chickens, or NRAMP1.

Age Factors↗
PubMed2000

Genetic background of Lewis negative blood group phenotype and its association with atherosclerotic disease in the NHLBI family heart study.

OBJECTIVES: To examine the prevalence of four mutations, T59G, T1067A, T202C and C314T, of the human alpha(1,3/1,4) fucosyltransferase 3 (FUT 3) gene amongst persons with Lewis negative and those with Lewis positive blood group phenotype. An additional objective was to explore the hypothesis that these mutations are associated with coronary heart disease and inflammatory reaction. DESIGN: A population-based cross-sectional study. SETTING: Analysis of samples and data from the National Heart Lung and Blood Institute Family Heart Study. SUBJECTS: All Lewis (a-b-) participants (n = 136) and a sample of Lewis positive participants (n = 136) of the Family Heart Study; all were of Caucasian ethnicity. MAIN OUTCOME MEASURES: The prevalence of examined mutations by Lewis phenotype. RESULTS: The examined mutations were common and strongly associated with the Lewis (a-b-) phenotype. Accordingly, 90-95% of Lewis (a-b-) individuals amongst Caucasians can be identified by screening for these four mutations. Exploratory analyses suggested that with the exception of T59G, all examined mutations were positively associated with prevalent coronary heart disease, although not statistically significantly, perhaps due to the small number of prevalent coronary heart disease cases. C-reactive protein tended to be higher amongst persons with a TC or CC genotype at position 202 (3.07 +/- 0.41 vs. 2.08 +/- 0.32 mg L-1, P = 0.06). CONCLUSIONS: Four specific mutations of fucosyltransferase 3 gene are responsible for the vast majority of Lewis (a-b-) phenotypes in Caucasians. These mutations are common in the population at large and may be associated with increased risk of coronary heart disease. Further studies using larger samples are warranted.

Arteriosclerosis↗
PubMed2002

Lung pathology in platelet-derived growth factor transgenic mice: effects of genetic background and fibrogenic agents.

We previously developed transgenic mice expressing human platelet-derived growth factor B chain (PDGF-B) from the lung-specific surfactant protein C (SPC) promoter. These mice developed enlarged airspaces, inflammation, and fibrosis of varying severity. In the present study we examined potential causes of this phenotypic variation and tested whether constitutive PDGF-B expression exacerbated fibrosis induced by bleomycin and silica. The SPC-PDGFB transgene construct was modified by replacement of the PDGF-B 3' UTR, which contains motifs known to mediate instability in other cytokine genes, with SV40 sequences containing an intron and polyadenylation signal. This modification resulted in an increase in the efficiency with which the construct was expressed, but no difference in lung pathology was observed compared to the original construct. Backcrossing of mice carrying the original SPC-PDGFB construct to C57BL/6 and SJL inbred strains resulted in a more severe phenotype in SJL-bred mice compared to C57BL/6-bred mice after 4 generations. To determine whether SPC-PDGFB transgenic mice had increased susceptibility to fibrogenic agents, the mice were treated with bleomycin or silica. No significant differences were detected in lung weight, hydroxyproline content, or histopathologic changes between transgenic and wild-type mice after bleomycin or silica treatment. These results demonstrate that the amount of PDGF-BB produced in wild-type mice is not a limiting factor in the development of bleomycin- or silica-induced pulmonary fibrosis.

Animals↗
PubMed1996

Multiplicity of genetic backgrounds among vancomycin-resistant Enterococcus faecium isolates recovered from an outbreak in a New York City hospital.

A total of 182 vancomycin-resistant Enterococcus faecium and 6 Enterococcus faecalis inpatient isolates recovered during a 2-year period (1990-1992) in a New York City hospital were analyzed by molecular fingerprinting techniques, pulsed-field gel electrophoresis (PFGE), of chromosomal SmaI digests combined with Southern hybridization using vanA and vanB2-specific DNA probes. Of the 180 isolates hybridizing with these probes, 153 carried the vanA and 27 the vanB gene. As many as 21 different PFGE types and a total of 54 subtypes were identified among the isolates, and the size of vanA and vanB-hybridizing DNA fragments also showed a wide range of sizes, from about 37 to over 280 kb (in vanA) or 140 kb (in vanB), suggesting extensive recombination, including chromosomal integration, of the resistance genes in the isolates. Close to one-third, 46, of the 148 isolates from 1992 belonged to two closely related PFGE subtype variants, each of which carried a 48 kb vanA hybridizing DNA fragment. Spread of this clone appears to be mainly responsible for the substantial increase in the prevalence of vancomycin-resistant E. faecium in early 1992.

Anti-Bacterial Agents↗
PubMed1988

High susceptibility of an analbuminemic congenic strain of rats with an F344 genetic background to induced bladder cancer and its possible mechanism.

The susceptibility of an analbuminemic congenic strain of rats (F344-alb) originating from the F344 strain to N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. F344-alb rats were found to be highly susceptible to induction of urinary bladder cancers. The incidences of bladder cancers in F344-alb and F344 rats were 94% (15/16) and 31% (5/16) in males and 100% (16/16) and 19% (3/16) in females. The bladder weights of these rats, including tumors, were 307 +/- 294 mg, 123 +/- 26 mg, 183 +/- 80 mg and 93 +/- 11 mg, respectively. Administration of 0.05%, 0.1% and 0.3% BBN in the drinking water for 2 weeks resulted in greater increases in the bladder content of N-butyl-N-(3-carboxypropyl)nitrosamine in F344-alb rats than in F344 rats. This increase was prevented by the presence of rat albumin.

Animals↗
PubMed1993

Rh null phenotypes are not due to a gross deletion and can occur on different Rh genetic backgrounds.

Alu element-primed PCR was performed on genomic clones containing human RH blood group genes. When used as a probe, the Alu PCR product detected a restriction fragment-length polymorphism which is in complete linkage disequilibrium with the Rh C/c serological polymorphism, irrespective of the Rh D or E serological type it is coupled with. This provides the opportunity to type individuals for their RH C gene directly at the DNA level. RFLP analysis of two individuals with the amorph Rh null phenotype revealed that in one case this phenotype occurred on an RH C background, whereas in the other it was on an RH c background. Taken together these results indicate that the Rh C/c polymorphism has arisen only once, but that the amorph Rh null phenotype, although exceedingly rare, is the result of at least two independent mutations.

Alleles↗
PubMed2001

Importance of the host genetic background on immune responses to Helicobacter pylori infection and therapeutic vaccine efficacy.

In order to investigate the role of host factors in Helicobacter pylori infection and immunity, two different strains of inbred mice, C57BL/6 and BALB/c, were infected with a standard H. pylori strain, SS1. A month later, infected mice were immunized orally with whole-cell lysates of H. pylori SS1 and cholera toxin on days 1, 3, 6, 30, and 54. Ten days after the last immunization, mice were sacrificed and the stomach was collected to assess H. pylori colonization density by quantitative culture. H. pylori SS1 colonization was significantly greater in C57BL/6 than in BALB/c (P<0.02 and P<0.003 at 2 and 13 weeks post-inoculation, respectively). Colonization in C57BL/6 persisted at equivalent levels for 13 weeks but the colonization density in BALB/c decreased significantly during this period. In contrast to the pattern of bacterial colonization, antibody responses following H. pylori SS1 infection were greater in BALB/c than in C57BL/6, suggesting that host factors may modulate the immune responses to H. pylori infection. Following therapeutic immunization, H. pylori colonization in BALB/c mice was also significantly reduced (P<0.03), while no significant differences in bacterial density were observed in C57BL/6. These observations collectively demonstrate the great importance of host factors in H. pylori infection and the development of effective immune responses.

Adjuvants, Immunologic↗
PubMed2004

Ethologically based resolution of D2-like dopamine receptor agonist-versus antagonist-induced behavioral topography in dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kDa "knockout" mutants congenic on the C57BL/6 genetic background.

Given the critical role of dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein of 32 kDa (DARPP-32) in the regulation of dopaminergic function, DARPP-32-null mutant mice congenic on the inbred C57BL/6 strain for 10 generations were examined phenotypically for their ethogram of responsivity to the selective D2-like receptor agonist RU 24213 (N-n-propyl-N-phenylethyl-p-3-hydroxyphenylethylamine) and the selective D2-like receptor antagonist YM 09151-2 (cis-N-[1-benzyl-2-methyl-pyrrolidin-3-yl]-5-chloro-2-methoxy-4-methylaminobenzamide), using procedures that resolve all topographies of behavior in the natural repertoire. After vehicle challenge, levels of sniffing and rearing seated were reduced in DARPP-32 mutants; the injection procedure seems to constitute a "stressor" that reveals phenotypic effects of DARPP-32 deletion not apparent under natural conditions. Topographical effects of 0.3 to 10.0 mg/kg RU 24213, primarily induction of sniffing and ponderous locomotion with accompanying reductions in rearing, grooming, sifting and chewing, were not altered to any material extent in DARPP-32-null mice. However, topographical effects of 0.005 to 0.625 mg/kg YM 09151-2, namely, reduction in sniffing, locomotion, rearing, grooming, and chewing but not sifting, were essentially absent in DARPP-32 mutants. Thus, the D2-like receptor agonist-mediated ethogram was essentially conserved, whereas major elements of the corresponding D2-like receptor antagonist-mediated ethogram were essentially absent in DARPP-32-null mice. This suggests some relationship between 1) extent of tonic dopaminergic activation of DARPP-32 mechanisms and 2) compensatory mechanisms consequent to the developmental absence of DARPP-32, which may emerge to act differentially on individual elements of the DARPP-32 system. Critically, the present data indicate that phenotypic effects of a given gene deletion using an agonist acting on the system disrupted cannot be generalized to a corresponding antagonist, and vice versa.

Animals↗
PubMed2005

Contributions of the viral genetic background and a single amino acid substitution in an immunodominant CD8+ T-cell epitope to murine coronavirus neurovirulence.

The immunodominant CD8+ T-cell epitope of a highly neurovirulent strain of mouse hepatitis virus (MHV), JHM, is thought to be essential for protection against virus persistence within the central nervous system. To test whether abrogation of this H-2Db-restricted epitope, located within the spike glycoprotein at residues S510 to 518 (S510), resulted in delayed virus clearance and/or virus persistence we selected isogenic recombinants which express either the wild-type JHM spike protein (RJHM) or spike containing the N514S mutation (RJHM(N514S)), which abrogates the response to S510. In contrast to observations in suckling mice in which viruses encoding inactivating mutations within the S510 epitope (epitope escape mutants) were associated with persistent virus and increased neurovirulence (Pewe et al., J Virol. 72:5912-5918, 1998), RJHM(N514S) was not more virulent than the parental, RJHM, in 4-week-old C57BL/6 (H-2b) mice after intracranial injection. Recombinant viruses expressing the JHM spike, wild type or encoding the N514S substitution, were also selected in which background genes were derived from the neuroattenuated A59 strain of MHV. Whereas recombinants expressing the wild-type JHM spike (SJHM/RA59) were highly neurovirulent, A59 recombinants containing the N514S mutation (SJHM(N514S)/RA59) were attenuated, replicated less efficiently, and exhibited reduced virus spread in the brain at 5 days postinfection (peak of infectious virus titers in the central nervous system) compared to parental virus encoding wild-type spike. Virulence assays in BALB/c mice (H-2d), which do not recognize the S510 epitope, revealed that attenuation of the epitope escape mutants was not due to the loss of a pathogenic immune response directed against the S510 epitope. Thus, an intact immunodominant S510 epitope is not essential for virus clearance from the CNS, the S510 inactivating mutation results in decreased virulence in weanling mice but not in suckling mice, suggesting that specific host conditions are required for epitope escape mutants to display increased virulence, and the N514S mutation causes increased attenuation in the context of A59 background genes, demonstrating that genes other than that for the spike are also important in determining neurovirulence.

Amino Acid Substitution↗
PubMed2005

A dominant interfering Bub1 mutant is insufficient to induce or alter thymic tumorigenesis in vivo, even in a sensitized genetic background.

Aneuploidy is a common feature of human tumors, often correlating with poor prognosis. The mitotic spindle checkpoint is thought to play a major role in aneuploidy suppression. To investigate the role of the spindle checkpoint in tumor suppression in vivo, we developed transgenic mice in which thymocytes express a dominant interfering fragment of Bub1, a kinase regulator of the spindle checkpoint. We report that, despite high-level expression of dominant-negative Bub1 (Bub1DN), a protein known to inhibit spindle checkpoint activity in cultured cells, thymocytes show no evidence of spindle checkpoint impairment. Transgenic animals also failed to show an increased predisposition to spontaneous tumors. Moreover, the Bub1DN transgene failed to alter the timing or characteristics of thymic lymphoma development in p53 heterozygous or homozygous null backgrounds, indicating that the lack of tumorigenesis is not due to suppression by p53-dependent checkpoints. These results indicate that overexpression of a Bub1 N-terminal fragment is insufficient to impair the spindle checkpoint in vivo or to drive tumorigenesis in the highly susceptible murine thymocyte system, either alone or in combination with G(1) checkpoint disruption.

Animals↗
PubMed2006

Genetic background of pancreatitis.

Trypsin activity is properly suppressed by pancreatic secretory trypsin inhibitor (PSTI), which is also known as serine protease inhibitor Kazal type 1 (SPINK1), thereby preventing damage to pancreatic acinar cells as a first line of defence. However, if trypsin activation exceeds the capacity of PSTI/SPINK1, a subsequent cascade of events leads to the activation of various proteases that damage cells. Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis. From analyses of hereditary pancreatitis and the phenotype of PSTI/SPINK1 (Spink3) knockout mice, we showed that the imbalance of trypsin activation and its inhibition by PSTI/SPINK1 would lead to the development of pancreatitis.

Animals↗