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Results for “genetic expression”

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At least 37 records · Page 2Linked to original sources
PubMed2026

Nonviral transposon‑engineered stem cells characterization: dose‑dependency between vector copy number and transgene expression.

Genetically engineered stem cells hold substantial promises for advancing regenerative medicine, yet ensuring their genomic safety remains a critical challenge. A key safety concern is vector copy number (VCN), which defines the number of integrated transgene copies per genome. Although ddPCR is used to assess VCN in virally transduced cells, its application in transposon‑engineered systems is limited. In this study, we extended VCN determination to non‑viral, transposon‑engineered stem cells. In alignment with FDA recommendations, the primary objective was to establish a robust and quantitative framework for interim VCN determination at the time of lot release. Specifically, we demonstrate that reliable interim VCN estimates increase in a dose‑dependent manner with increasing plasmid input. In addition, strong linear correlations between VCN and both EGFP median fluorescence intensity (MFI) and gene‑of‑interest (GOI) protein expression validate the accuracy of this framework. Furthermore, comparison of two distinct GOIs revealed gene‑specific differences in expression efficiency. Together, these findings validate a standardized VCN determination workflow that quantitatively links plasmid dose, genomic integration, and functional transgene expression. This workflow provides a systematic characterization of engineered cells, offering comprehensive information to support downstream risk‑based analyses to ensure the genomic safety and stability of the final cell product.

Transgenes↗
PubMed1978

Role of B cells in the expression of genetic resistance to growth of Rous sarcoma in the chicken.

Resistance to the development of progressively growing tumors induced by Rous sarcoma virus is a dominant trait controlled by a gene linked to the major histocompatibility complex (MHC). The effect of bursectomy (Bx) on the expression of this trait was studied in two inbred lines of chickens homozygous for different MHC alleles, and which differ with respect to the gene controlling resistance to Rous tumors. The results show that Bx alters the expression of the trait, since genetically resistant birds were rendered highly susceptible to progressive tumor growth. The bursa of Fabricius thus makes an important contribution to resistance. The results do not indicate whether genetic resistance is mediated exclusively by B cells or by another bursa-dependent population.

Animals↗
PubMed1992

Biological adaptation of the myocardium to a permanent change in loading conditions.

Cardiac hypertrophy due to permanent mechanical overloading is only one example among thousands of the general process of biological adaptation. The process is randomly governed and results in at least one thermodynamical benefit: to be adaptational and to induce several changes in gene expression. Some of these changes are detrimental, some can even be useless. The cascade of events which finally leads to a permanent modification of the genetic expression involves an initial signal, likely to be the stretch, a pathway which transducts the signal, and a transient change in genetic expression which transmits competence to the cell to be transformed. The permanent modifications occur at all cellular levels including the sarcomere, sarcolemma, energy metabolism, and extra-cellular matrix, but they are species-specific and differ in the ventricles and the atria.

Adaptation, Physiological↗
PubMed1978

Resistance of visna virus to interferon.

Visna is a slow infection of sheep caused by a retrovirus. The persistence of virus despite the immune response of the host is best explained by restricted genetic expression of the virus and consequently prolonged periods of residence inside cells. The purpose of this investigation was to determine whether the restriction in genetic expression of visna virus is mediated by interferon. Sheep interferon induced by polyriboinosinic-polyribocytidylic acid in fetal lambs inhibited the growth of herpes simplex virus, vesicular stomatitis virus, and vaccinia virus, but even highly concentrated interferon did not affect the replication of visna virus in sheep choroid plexus cells. The same results were obtained whether the effects of interferon were assessed in single of multiple cycles of growth and when interferon was added at later times in the growth cycle of the virus. This unusual resistance of visna virus to interferon suggests that restriction of viral expression by the host is probably not mediated in this way.

Animals↗
PubMedDate not supplied

Allelic expression and genetic distance in hybrid macaque monkeys.

Levels of structural genic divergence at 21 loci encoding blood proteins were quantified in six macaque (Macaca) species, using standard techniques of starch-gel electrophoresis. Genetic distances between all pairs of species fall within a narrow range (0.080 less than or equal to D less than or equal to 0.250; D = 0.164) which is near the lower limit of genetic distances typically observed between other congeneric organisms. In an effort to measure levels of regulatory gene differences between these species, we have examined the patterns of allelic expression in their F1, F2, and backcross hybrids. Nine of the 21 loci examined encode allelic forms of the proteins with different electrophoretic mobilities in at least some of the individual parents of the hybrids. In all cases where expected, hybrids express fully both maternal and paternal allelic products, thus providing no strong evidence ofr a breakdown in the regulatory mechanisms responsible for proper expression of these genes. Results are compared to degrees of allelic repression previously observed in other hybrids, and are discussed within the context of current ideas about rates of regulatory gene evolution in mammals.

Alleles↗
PubMed2025

Validation of caprine H11 and the Rosa26 platform for transgene integration via CRISPR-based system: investigations on stable transgene expression and genetic biosafety.

CRISPR/Cas9 technology is an efficient tool for site-specific livestock gene editing. However, to minimize potential disruption of host genome function, exogenous genes should be integrated into well-characterized genomic loci, such as H11 or Rosa26, which have been empirically validated for stable transgene expression. This study established a multi-dimensional assessment system to evaluate the biological applicability of the H11 locus and the widely used Rosa26 targeting platform as sites for targeted integration of exogenous genes in goats. Donor cells carrying the enhanced green fluorescent protein (EGFP) reporter gene at the H11 and Rosa26 loci were generated via CRISPR/Cas9-mediated homology-directed repair; this was followed by somatic cell nuclear transfer to produce transgenic cloned embryos and healthy offspring. Multi-dimensional analyses revealed the following. At the cellular level, there was stable and efficient EGFP expression at integration sites, with donor cells maintaining normal cell cycle progression, proliferation capacity, and apoptosis levels, and with no alterations in the transcriptional integrity of adjacent genes. At the embryonic level, there was sustained EGFP expression across pre-implantation embryonic stages, with developmental metrics statistically indistinguishable from wild-type embryos. Finally, at the individual level, cloned offspring exhibited growth phenotypes consistent with wild-type counterparts, and EGFP showed broad-spectrum expression in eight tissues. This study establishes the first CRISPR/Cas9-based crossscale (cellular-embryonic-individual) validation in goats, demonstrating that the H11 and Rosa26 loci support efficient and stable transgene integration in goats. These results provide a precise and predictable technical framework for livestock genetic improvement.

Animals↗
PubMed1979

Strain-dependent differences in murine susceptibility to coccidia.

Differences in susceptibility of strains of mice to Eimeria ferrisi were observed by infecting eight strains of mice with six infectious dose levels and comparing the mortality rate among the strains for a period of 12 days. Mice of the C57BL/6 and HA/ICR strains were susceptible, and those of A/He, AKR, BALB/c, CBA, C3H/Anf, and DBA/2 strains were resistant to coccidial infection. Resistance was a dominant genetic expression, as indicated by the resistant response of F(1) hybrids of susceptible C57BL/6 and resistant CBA, C3H/Anf, or DBA/2 strains. An E. ferrisi infection in congenitally athymic nu/nu mice and phenotypically normal heterozygous nu/+ mice was used to determine how thymus-dependent immunoincompetence in cell-mediated immunity of the nu/nu mouse affected resistance to infection in a genetic background of the resistant BALB/c mouse. Results of primary and challenge infections in these two strains of mice suggested that resistance is thymus dependent. Furthermore, impairment of thymus-dependent cell-mediated immunity in resistant AKR mice by treatment with mouse antithymus serum led to partial susceptibility. However, susceptible C57BL/6 and HA/ICR strains are phenotypically normal mice, and previous evidence showed that C57BL/6 mice are not completely immunoincompetent in cell-mediated reactivity to coccidia. Collectively, our data show that cell-mediated immunity is necessary for resistance but may be subjected to modification by genetic expression of the host. The possible role of immune response genes in the control of coccidial immunity is discussed.

Animals↗
PubMed1976

Expression of genetic markers of erythrocyte immunoglobulin G autoantibodies in autoimmune hemolytic anemia.

The Gm allotype constitution of the autoantibody molecules and the serum Gm phenotypes were determined in 19 patients with autiommune hemolytic anemia of IgG type. The results showed that the known heterogeneity of the antierythrocyte autoantibodies in this disease concerns not only the immunoglobulin class and the isotypic subclass, but also the genetic markers of these molecules. Evidence was obtained that the anomalous production of antierythrocyte autoantibodies is polyclonal, that thse autoantibodies belong mainly to the IgG1 isotypic subclass, and that they have a preference for the Gm(1) allotype. In addition, certain of the findings point to a preferential expression of the Gm(1,21) haplotype.

Anemia, Hemolytic, Autoimmune↗
PubMed1992

Facial expressions and genetic sensitivity to 6-n-propylthiouracil predict hedonic response to sweet.

Individuals differ in their hedonic response to sweet: sweet likers show increasing liking with increasing sucrose concentration, while sweet dislikers show increasing dislike with increasing concentration. Our results indicated that naive raters can correctly classify sweet likers and dislikers by observing subjects' facial responses to the taste of sucrose. Also, for both adults and children, the sweet liker/disliker distinction correlated strongly with the genetically determined ability to taste 6-n-propylthiouracil (PROP): PROP nontasters were almost always sweet likers, whereas sweet dislikers were almost always PROP tasters. Sweet dislikers also reported a purer sweet sensation than likers, who perceived nonsweet components in pure sucrose solutions. These results suggest that the sweet liker/disliker distinction is robust and valid, and that sensitivity to PROP may influence preference for sweet by altering the quality of sweet.

Adolescent↗
PubMed2025

A single-locus quantitative genetic model incorporating DNA methylation.

We describe a single-locus quantitative genetic model that incorporates effects due to DNA methylation. Extending Fisher's decomposition of the genotypic value, we distinguish two quantities to predict an individual's phenotypic or genetic values: the "basic genetic value" and the "expressed genetic value". We show how these quantities relate to the concept of breeding value and derive their corresponding formulas, along with those for phenotypic variance and covariance between relatives. The resulting parameters are influenced by several factors, including the population distribution of DNA methylation levels, the functional relationship between methylation and phenotype, the magnitudes of genetic and methylation effects, and allele frequencies. We show that under the conditions modeled, the presence of DNA methylation does not bias estimated breeding values.

DNA Methylation↗
PubMed1992

Alpha-6 (CD 49f) integrin expression in genetic and acquired bullous skin diseases. A comparison of its distribution with bullous pemphigoid antigen.

Bullous pemphigoid (BP) antigen and alpha 6 integrin are hemidesmosome-associated glycoproteins of basal keratinocytes. In this work, the immunoreactivity of antibodies to BP and to alpha 6 in salt- or dispase-split human skin, and in 46 biopsy specimens of various genetic and autoimmune bullous dermatoses taken from various body sites, was studied by double-labeling immunofluorescence. In all specimens, both antigens localized at the same side of the blisters observed, i.e. the roof of the bulla in cases with a junctional or dermolytic cleavage, or the floor of the blister in those with intraepidermal cleavage. Immunostaining for alpha 6 was strong and present in all specimens studied, whereas the one obtained with the BP serum was absent from some specimens. These results show that the BP antigen and the alpha 6 integrin colocalize at the level of cleavage in bullous diseases; however, the more consistent and reproducible reactivity obtained with the anti-alpha 6 antibody suggests that this should be preferentially used in the immunohistochemical investigation of bullous dermatoses.

Antigens, Surface↗