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Biomedical subjects

G Harold

Publications and source records attributed to G Harold.

7 recordsLinked to original sources
PubMed1998

Life events and depressive symptoms in childhood--shared genes or shared adversity? A research note.

A twin study design was used to examine to what extent genetic and environmental factors mediate the association between life events and depressive symptoms. Questionnaire measures (maternally rated) of depressive symptoms and life events were obtained for a systematically ascertained sample of 270 twin pairs aged 8 to 17 years. Bivariate genetic model fitting showed that depressive symptoms and some life events (total events, negative impact) share a common genetic influence. The covariation of independent life events and depressive symptoms was explained by a shared environmental influence common to both. At least part of the association between life events and depressive symptoms is mediated by familial factors that include both genes and shared environment.

Adaptation, Psychological↗
PubMed1997

Mammalian cDNA and prokaryotic reporter sequences silence adjacent transgenes in transgenic mice.

The ovine beta-lactoglobulin gene is expressed efficiently and at high levels in the mammary gland of transgenic mice. In contrast, when this gene is linked to a second gene construct comprising a mammalian cDNA or a CAT reporter sequence it fails to be expressed in the majority of transgenic lines generated. We suggest that mammalian cDNAs and prokaryotic reporter sequences can serve as active foci for gene silencing in the mammalian genome.

Animals↗
PubMed1997

Transgene rescue in the mammary gland is associated with transcription but does not require translation of BLG transgenes.

Many transgenes, particularly those comprising cDNA sequences fail to be expressed when they are introduced into transgenic mice. We have previously shown that this problem can be overcome in the mammary gland by co-integrating a poorly expressed cDNA transgene, comprising the sheep beta-lactoglobulin promoter, with the efficiently expressed, unmodified beta-lactoglobulin gene. In this report we demonstrate that the transcription of the beta-lactoglobulin gene is associated with this effect because co-integration with a non-transcribed beta-lactoglobulin gene fails to rescue expression. By contrast, co-integration with a translationally inactivated beta-lactoglobulin transgene does rescue the expression of the second gene, but without the co-production of beta-lactoglobulin protein.

Animals↗
PubMed1997

Selective cell ablation in transgenic mice expression E. coli nitroreductase.

The gene encoding E. coli nitroreductase (NTR) was expressed in the luminal cells of the mammary gland of transgenic mice using the ovine beta-lactoglobulin promoter. Treatment of NTR expressing animals with the prodrug CB1954 (5-aziridin-1-yl-2-4-dinitrobenzamide) resulted in a rapid and selective killing of this population of cells whereas the closely associated myoepithelial cells were unaffected. NTR-mediated inducible cell ablation offers a number of advantages over the use of HSV1-tk for the selective killing of cells in vivo.

Animals↗
PubMed1995

Fixing human factor IX (fIX): correction of a cryptic RNA splice enables the production of biologically active fIX in the mammary gland of transgenic mice.

Transgenic mice and sheep secrete only low levels of human factor IX in their milk because of an aberrant splicing of the transgene RNA in the mammary gland. Removal of the cryptic 3' splice site prevents this splicing and leads to the production of relatively high levels of factor IX. The purified protein is fully active showing that the mammary gland is capable of the efficient post-translational modification of this protein and that transgenic animals are a suitable means of its production.

Animals↗
PubMed1993

Transgenic animal methodologies and their applications.

In the past 10 years the capacity has been acquired to genetically transform mammals via insertion of genes into developmentally totipotent embryonic cells. This profound advance has impacted significantly on our understanding of basic mechanisms of gene regulation, and has enabled practitioner's of this "transgenic technology" to establish important paradigms for the genetic engineering of experimental animals and livestock. The two most powerful forms of genetic engineering to emerge from this research include the targeted expression of foreign genes, or transgenes, and the ability to target specific endogenous mouse genes for mutagenesis. In this presentation I will outline the general principles underlying this technology, and provide examples of its use in research on cancer and aging that are ongoing in our laboratory.

Aging↗