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At least 307 records · Page 17Linked to original sources
PubMed1988

T-cell receptor gene rearrangement in primary tumors: effect of genetic background and inducing agent.

The status of T-cell receptor beta and gamma genes has been assessed in a series of primary tumors induced by a chemical carcinogen or by gamma-irradiation using two inbred strains of mice. It appears that these well-characterized regimens of carcinogenesis yield T-cell tumors showing gene rearrangements consistent with a clonal origin of the tumors. Individual rearranged bands seem to represent orthodox, intralocus recombination events. A variety of rearrangement phenotypes are observed, most strikingly for the gamma genes, and differences in the degree of T-cell receptor gene rearrangements observed can be categorized according to the inducing agent and to the genetic background of the mice, with the implication that premalignant thymocytes have been captured in different stages of T-cell development. Additionally, primary tumors were shown to express significant levels of mature beta gene mRNA.

Animals↗
PubMed1990

Effect of genetic background on cosegregation of renin alleles and blood pressure in Dahl rats.

The cosegregation of renin alleles and blood pressure was evaluated in segregating populations derived from inbred Dahl salt hypertension sensitive (S) and inbred Dahl salt hypertension resistant (R) rats. The populations were raised on high salt diet (8% NaCl). In F2 and F1 X S populations, there was a significant positive gene-dosage relationship between the S-rat renin allele and blood pressure. In contrast, no such relationship was seen in the F1 X R population. Since in the F1 X R population the genetic background is strongly influenced by genes from the R rat (75% R, 25% S), the result is interpreted to mean that genes at other (unidentified) loci modify the blood pressure effect of the S-rat renin allele.

Alleles↗
PubMed2003

Pharmacogenetics of cytochrome p4502D6: genetic background and clinical implication.

Interindividual differences in the pharmacokinetics of a number of drugs are often due to hereditary polymorphisms of drug-metabolizing enzymes. Most important is cytochrome p4502D6 (CYP2D6), also known as debrisoquine/sparteine hydroxylase. It catalyzes hydroxylation or demethylation of more than 20% of drugs metabolized in the human liver, such as neuroleptics, antidepressants, some beta-blockers and many others like codeine. About 7%-10% of Caucasians lack any CYP2D6 activity due to deletions and frame-shift or splice-site mutations of the gene. About 1%-3% of Middle-Europeans, but up to 29% of Ethiopians display gene duplications, leading to elevated so-called ultrarapid metabolization rates. Meanwhile there is now a much better understanding of the genetic background of poor, intermediate, extensive and ultrarapid metabolizers, enabling a more precise DNA genotyping-based prediction of plasma levels. Since there is evidence that deteriorated drug elimination partly accounts for drug side-effects, CYP2D6 genotyping could contribute to an individualized and therefore optimized drug therapy.

Cytochrome P-450 CYP2D6↗
PubMed1982

Comparative levels of endogenous myelin basic protein-serum factors (MBP-SFs) in adult and suckling mice (B6CBAF1 and B6C3HF1, strains) and in neurologically mutant mice of the same genetic background.

Normal adult B6C3HF1 and B6CBAF1 mice contained at least 10 times higher levels (1.17 microM) of endogenous myelin basic protein-serum factors (MBP-SFs) than previously found in adult Lewis rats. In rat MBP-SF levels in the adult (0.03 microM) were much less than in the suckling animals (0.74 microM). In mice, by contrast, the adult (1.17 microM) and suckling (0.75 microM) levels were similar. Suckling mice from 9 different neurologically mutant strains and their clinically normal littermates had MBP-SF levels (0.5 microM) slightly below that of normal suckling mice of the same genetic background (0.75 microM).

Animals↗
PubMed2004

Preservation of eumelanin hair pigmentation in proopiomelanocortin-deficient mice on a nonagouti (a/a) genetic background.

The original strain of proopiomelanocortin (POMC)-deficient mice (Pomc-/-) was generated by homologous recombination in 129X1/SvJ (A(w)/A(w))-derived embryonic stem cells using a targeting construct that deleted exon 3, encoding all the known functional POMC-derived peptides including alpha MSH, from the Pomc gene. Although these Pomc-/- mice exhibited adrenal hypoplasia and obesity similar to the syndrome of POMC deficiency in children, their agouti coat color was only subtly altered. To further investigate the mechanism of hair pigmentation in the absence of POMC peptides, we studied wild-type (Pomc+/+), heterozygous (Pomc+/-), and homozygous (Pomc-/-) mice on a nonagouti (a/a) 129;B6 hybrid genetic background. All three genotypes had similar black fur pigmentation with yellow hairs behind the ears, around the nipples, and in the perianal area characteristic of inbred C57BL/6 mice. Histologic and electron paramagnetic resonance spectrometry examination demonstrated that hair follicles in back skin of Pomc-/- mice developed with normal structure and eumelanin pigmentation; corresponding molecular analyses, however, excluded local production of alpha MSH and ACTH because neither Pomc nor putative Pomc pseudogene mRNAs were detected in the skin. Thus, 129;B6 Pomc null mutant mice produce abundant eumelanin hair pigmentation despite their congenital absence of melanocortin ligands. These results suggest that either the mouse melanocortin receptor 1 has sufficient basal activity to trigger and sustain eumelanogenesis in vivo or that redundant nonmelanocortin pathway(s) compensate for the melanocortin deficiency. Whereas the latter implies feedback control of melanogenesis, it is also possible that the two mechanisms operate jointly in hair follicles.

Adrenal Glands↗
PubMed2007

Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion-sensitive and promotion-resistant genetic backgrounds.

Elevated polyamine content and increased ornithine decarboxylase (ODC) activity have been associated with neoplastic growth in numerous animal models and human tissues. Antizyme (AZ) is a negative regulator of polyamine metabolism that inhibits ODC activity, stimulates ODC degradation, and suppresses polyamine uptake. Preliminary evidence, obtained from transgenic mice with tissue specific overexpression of AZ indicates that tumor development can be suppressed by AZ. To extend these studies, we have examined the effect of keratin 5 (K5)- or K6-driven AZ transgenes on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical carcinogenesis of the skin, in promotion-resistant C57BL/6 and promotion-sensitive DBA/2 mice. On both genetic backgrounds, K6-AZ mice showed a reduction in tumor multiplicity, with 85% fewer tumors than wild-type controls on the C57BL/6 background and 50% fewer tumors on the DBA/2 background. K5-AZ mice developed 50% fewer tumors than controls on both backgrounds. The percent of mice with tumors and tumor size were also reduced in the K5-AZ and K6-AZ groups. Tumor and TPA-treated skin sections from K6-AZ mice exhibited the strongest AZ expression, with localization mainly in suprabasal keratinocytes. K6-AZ mice also had slightly reduced cell proliferation rates in tumors and TPA-treated skin. The lack of a more pronounced effect on cell proliferation is probably explained by the observation that AZ staining did not colocalize with proliferating cell nuclear antigen (PCNA), a marker for the proliferative compartment. These studies demonstrate a tumor-suppressive effect of AZ in C57BL/6 and DBA/2 mice, and confirm the importance of ODC and polyamines in tumor development.

Animals↗
PubMed2003

Congenic D1A dopamine receptor mutants: ethologically based resolution of behavioural topography indicates genetic background as a determinant of knockout phenotype.

D(1A)-null mice were backcrossed over 14 generations into a C57BL/6 background to result in essential elimination (to <0.005%) of any contribution from the 129/Sv component of their initially mixed (129/SvxC57BL/6) background. Their phenotype was assessed using an ethologically based approach that resolves each individual topography of behaviour in the natural repertoire. Habituation of sniffing, locomotion, rearing seated, and rearing to wall in wild types over several hours was profoundly retarded in congenic D(1A) mutants; conversely, rearing free and sifting were essentially abolished. Resultant increases in individual topographies of behaviour were substantially greater in congenic D(1A) mutants than in those on a mixed background. This phenotype was little altered by the selective D(1)-like antagonist SCH 23390 and could not be blocked by the selective D(2)-like antagonist YM 09151-2. The selective D(1)-like agonist SK&F 83959 could not further elevate those behaviours already heightened in congenic D(1A) mutants, while the induction of stereotyped sniffing and plodding locomotion by the selective D(2)-like agonist RU 24213 was disrupted. Genetic background appears to modulate critically the magnitude but not the general nature of the D(1A)-null phenotype, which may involve compensatory processes independent of other D(1)-like or D(2)-like receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

[Genetic mapping of resistant gene to southern corn rust and the tagging analysis on different genetic background].

Southern corn rust (SCR) is a destructive disease in maize. The inbred line Qi319 is highly resistant to southern corn rust. SSR technique was employed to preliminary mapping of the resistance gene. Bulked segregant analysis revealed that two primers, phi 118 and phi 041, amplified polymorphic bands. SSR analysis on populations indicated the two primers were linked to the rust resistance gene, which was mapped on the short arm of chromosome 10. In addition, comparative analysis of the amplification bands among different populations revealed that the amplification products with the same primer in different populations were dissimilar. This result indicates that the genetic background may affect results of gene mapping and tagging. So, it is important to select suitable population to performing molecular marker analysis and gene mapping.

Basidiomycota↗
PubMed1996

Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone genetic background in relation to Fas-defect MRL/1pr mice.

The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis, this defect results in CD4-CD8- double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr mutation and is almost normal during the first 6 mo of life. The lpr mutation, however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice. These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.

Aging↗
PubMed2001

Genotype-by-environment interaction with broiler genotypes differing in growth rate. 1. The effects of high ambient temperature and naked-neck genotype on lines differing in genetic background.

High ambient temperature (AT) significantly depresses growth rate and meat yield of commercial broilers, thus making it a major factor hindering poultry meat production, especially in hot climates. The effects of high AT were variably moderated when feather coverage was reduced by the naked-neck gene (Na). In this study, the effects of high AT and Na were investigated in broiler progeny of hens from a sire line and two dam lines, differing in growth rate and meat yield due to different breeding histories. Heterozygous naked-neck (Na/na) males were mated with normally feathered (na/na) hens from the three lines. The 500 progeny were segregated for Na/na and na/na genotypes. After brooding, chicks of each maternal background, Na genotype, and sex were equally divided to two similar chambers and were reared on litter to 53 d of age. One chamber was set to normal AT, averaging 25 C; the second chamber was set to high AT, averaging 30 C. The high AT treatment reduced growth and meat yield in the progeny of all three groups. This reduction increased with age and was highest in the broilers produced by hens from a sire line bred for high growth rate and breast meat yield. The two other groups, produced by hens from selected and relaxed dam lines, differed in growth rate but were similarly affected by the high AT. It is suggested that the magnitude of the high AT effect depends not only on differences in potential growth rate but also on differences in overall genetic background. It was also shown that broiler performance in the final weeks could be improved by introducing the Na gene into commercial flocks. The advantage of the Na/na genotype was much more pronounced at high AT and in broilers with genetically higher growth rate and breast meat yield.

Animals↗
PubMed2001

Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice.

Sensitivity to cadmium (Cd)-induced testicular injury varies greatly among mouse strains. For instance, 129/SvJ (129) mice are highly sensitive while C57BL/6J (C57) mice are refractory to Cd-induced testicular injury. Metallothionein (MT), a Cd-binding protein, is thought to be responsible for the strain susceptibility to Cd toxicity. In this study, MT-I/II knockout (MT-null) and wild-type 129 mice were used to determine the role of MT in Cd-induced testicular injury. Two additional strains of mice (C57 and the C57 x 129 F1cross) were also used to help define the role of genetic background in Cd toxicity. Mice were given 5-20 micromol/kg ip CdCl(2) and testicular injury was examined 24 h later by histopathology and testicular hemoglobin concentration. Cd produced dose-dependent testicular injury in all strains of mice, except for C57 mice, in which testicular injury could not be produced. MT-null mice were more sensitive than C57 x 129 mice but were equally sensitive as 129 mice to Cd-induced testicular injury. Fourteen days after 15 micromol/kg ip Cd administration, testicular atrophy was evident in MT-null, 129, and C57 x 129 mice but was absent in C57 mice. The resistance of C57 mice to Cd-induced testicular injury could not be attributed solely to a decreased uptake of (109)Cd nor to a greater amount of testicular MT. Microarray analysis revealed a higher expression of glutathione peroxidase in the testes of C57 mice, as well as genes encoding antioxidant components and DNA damage/repair, but their significance to Cd-induced injury is not immediately clear. Thus, this study demonstrates that it is genetic strain, not MT genotype, that is mechanistically important in determining susceptibility to Cd-induced testicular injury.

Animals↗
PubMed2001

Multilocus sequence typing of Streptococcus pneumoniae clones with unusual drug resistance patterns: genetic backgrounds and relatedness to other epidemic clones.

Six drug-resistant Streptococcus pneumoniae clones were previously identified from day care centers in Portugal, primarily on the basis of common pulsed-field gel electrophoresis (PFGE) patterns. These clones were susceptible to penicillin or had only very low-level resistance to it (most MICs, < or =0.25 microg/mL) and accounted for a large proportion (35%) of all drug-resistant pneumococci colonizing the nasopharynx of healthy children attending day care. Five of the 6 clones were identified among pneumococcal clinical isolates collected in other countries. In this study, we applied multilocus sequence typing (MLST) to describe the genetic background of these clones. MLST confirmed previous findings obtained by PFGE and allowed for the extension of the international clonal relationships by showing that each of the 6 clones was internationally disseminated and was able to cause pneumococcal disease.

Anti-Bacterial Agents↗
PubMed2005

Expression of high-level methicillin resistance in Staphylococcus aureus from the Staphylococcus sciuri mec A homologue: role of mutation(s) in the genetic background and in the coding region of mec A.

A close homologue of the mec A gene, the primary drug resistance determinant in methicillin resistant Staphylococcus aureus (MRSA), is ubiquitous in the animal commensal species Staphylococcus sciuri, yet most isolates of this staphylococcal species are susceptible to beta-lactam antibiotics including methicillin. Recently, we showed that in a methicillin-resistant mutant of S. sciuri prepared in the laboratory, the mec A homologue is converted to an antibiotic resistance gene by a point mutation introduced into the -10 consensus of the promoter and such promoter-up mutants of the S. sciuri mec A can express a significant degree of methicillin resistance when introduced into an antibiotic-susceptible strain of S. aureus. We now demonstrate that in this system further increase of the drug resistance phenotype may be achieved under antibiotic pressure by at least two different mechanisms. The first one of these involves the introduction of a point mutation at nucleotide Nt 1889 in the coding region of the S. sciuri-derived mec A determinant, resulting in the replacement of an asparagine with a threonine residue downstream of the conserved SXXK motif which causes extensive reduction in the beta-lactam antibiotic binding capacity (affinity) of the penicillin binding protein (PBP) encoded by the S. sciuri mec A homologue. A second, distinct, mechanism causing increased methicillin resistance is associated with mutation(s) of unknown nature in the genetic background of the S. aureus host.

Bacterial Proteins↗
PubMed2002

Differential spectrum of mutations that activate the Escherichia coli bgl operon in an rpoS genetic background.

The bgl promoter is silent in wild-type Escherichia coli under standard laboratory conditions, and as a result, cells exhibit a beta-glucoside-negative (Bgl-) phenotype. Silencing is brought about by negative elements that flank the promoter and include DNA structural elements and sequences that interact with the nucleoid-associated protein H-NS. Mutations that confer a Bgl+ phenotype arise spontaneously at a detectable frequency. Transposition of DNA insertion elements within the regulatory locus, bglR, constitutes the major class of activating mutations identified in laboratory cultures. The rpoS-encoded sigmaS, the stationary-phase sigma factor, is involved in both physiological as well as genetic changes that occur in the cell under stationary-state conditions. In an attempt to see if the rpoS status of the cell influences the nature of the mutations that activate the bgl promoter, we analyzed spontaneously arising Bgl+ mutants in rpoS+ and rpoS genetic backgrounds. We show that the spectrum of activating mutations in rpoS cells is different from that in rpoS+ cells. Unlike rpoS+ cells, where insertions in bglR are the predominant activating mutations, mutations in hns make up the majority in rpoS cells. The physiological significance of these differences is discussed in the context of survival of natural populations of E. coli.

Bacterial Proteins↗
PubMed2006

Effects of age-related hearing loss on startle reflex and prepulse inhibition in mice on pure and mixed C57BL and 129 genetic background.

The present study examined the developmental course of the age-related hearing loss and its consequences on the expression of acoustic startle reflex (ASR) and prepulse inhibition (PPI) generated by white-noise bursts in 129S2/SvPas (129) and C57BL/6J (C57) mouse strains and their F(1) hybrids. Auditory brainstem responses (ABR), ASR and PPI were assessed at various time points: 6, 28, 41 and 94 weeks. Both parental strains showed marked ABR threshold shifts with age, with C57 mice having the most pronounced deficits. By contrast, the hybrids displayed only minor hearing loss with age. The time courses of ASR and PPI varied considerably between the mouse strains. From 6 to 41 weeks of age, ASR and PPI elicited by weak stimuli (70-90dB) increased in C57 mice, whereas the startle responses to intense stimuli (95-120dB) declined progressively. In 129 and hybrid mice, PPI levels remained relatively stable during the first year, but a progressive increase of ASR was observed in the hybrids for intense stimuli (95-120dB). When animals reached 94 weeks of age, marked deterioration of ASR was observed in all strains, while deficits in PPI were only seen in 129 and C57 mice. These findings show that the time course and the severity of the hearing loss vary considerably between 129, C57 strains and their hybrids, thus suggesting a marked heterogeneity in the genetic mechanisms underlying deafness in mice. They also demonstrate that the age-related hearing loss may have complex consequences on auditory behavioral performances depending of the severity of the deficits, the genetic background as well as the stimuli parameters.

Acoustic Stimulation↗
PubMed1991

Frequency and genetic background of the position 122 (Val----Ile) variant transthyretin gene in the black population.

Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals. To estimate the frequency of the MaeIII(-) gene in the black population without overt cardiac disease, DNA from 177 black individuals without amyloidosis was amplified by the PCR around TTR codon 122 and was digested with MaeIII. The MaeIII(-) gene frequency was 4/354 (1.1%; 95% confidence interval 0.32%2.7%), suggesting that the variant is relatively common in blacks. HLA genotype testing did not suggest that the TTR (122 Val----Ile) heterozygotes were of a closely related genetic background.

Amino Acid Sequence↗
PubMed1985

[Cerebral palsy--investigation of its causal factors and genetical background].

In the last 30 years the prevalence rate of cerebral palsy (CP) has remarkably decreased in Japan. The decrease is arbitrarily attributed to the reduced frequency of such risk factors for CP, as low birthweight, severe asphyxia, and kernicterus in the neonatal period. However, there is no statistical data providing the evidence that CP patients complicating these risk factors have actually decreased so far. In order to make clear the bases of the decrease in prevalence of CP, we examined the changing patterns in the suggested cause of CP, experienced in the last 30 years. The investigation included the maternal condition of pregnancy and delivery, in relation to the neonatal risk factors, and genetic background of the family. In CP, low birthweight babies of 2500 gm or less were common (36.9%) and the mean birthweight (2689 gm) was obviously smaller than that of general population. In spite of the constant decline of the incidence of low birthweight babies in the general population in the last 30 years, the ratio of low birthweight to total births in CP group had not changed in this study period. It was concluded that the low birthweight following premature birth is still an important predisposing factor of CP. Asphyxia was frequently seen in the CP population. The rate of asphyxia was significantly higher in the group with a normal birthweight more than 2501 gm (58.4%), or gestational weeks longer than 36 weeks (57.7%), comparing with that of low birthweight (41.1%), or premature (40.7%) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia Neonatorum↗
PubMed2004

Host genetic background determines whether IL-18 deficiency results in increased susceptibility or resistance to murine Leishmania major infection.

Interleukin-18 (IL-18) plays an important role in innate and acquired immunity. IL-18 gene deficient (IL-18-/-) mice of the 129 x CD1 strain were reported to be more susceptible to Leishmania major infection than the wild-type mice. In contrast IL-18-/- mice of the C57BL/6 background were found to be as resistant as the wild-type (WT) mice. To resolve this discrepancy, IL-18 gene deficiency was introduced by backcrossing on to the highly susceptible BALB/c, or the moderately resistant DBA/1 backgrounds. Here we have demonstrated that BALB/c IL-18-/- mice were more resistant to L. major infection than WT BALB/c mice, whereas DBA/1 IL-18-/- mice were markedly more susceptible than their WT littermates. BALB/c IL-18-/- mice produced less IFNgamma and IL-4, whereas DBA/1 IL-18ko mice produced more IFNgamma and IL-4 than their respective WT controls. These result clearly demonstrate that the role of IL-18 in resistance or susceptibility to L. major is determined by host genetic background.

Animals↗