Biomedical subjects

M L Hooper

Publications and source records attributed to M L Hooper.

75 records · Page 5Linked to original sources

PubMedDate not supplied

129/Ola mice carrying a null mutation in PrP that abolishes mRNA production are developmentally normal.

The neural membrane glycoprotein PrP is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of PrP and its precise role in disease are not understood. Recently, gene targeting has been used to produce mice with neo/PrP fusion transcripts, but no detectable PrP protein in the brain (1). Here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both PrP protein and mRNA sequences. At 7 mo of age, these mice show no overt phenotypic abnormalities despite the normal high levels of expression of PrP during mouse development. The mice are being used in experiments designed to address the role of PrP in the pathogenesis of scrapie and the replication of infectivity.

Aging↗

PubMedDate not supplied

In vitro effect of platelet-derived growth factor on fibroproliferation and effect of cytokine antagonists.

Platelet-derived growth factor (PDGF) stimulates fibroblast proliferation and increases collagen synthesis. Fibroproliferation, as assessed by tritiated thymidine uptake, was significantly stimulated by platelet-derived growth factor (8 ng/ml). Several drugs including dexamethasone (1 nM-20 microM), cysteamine (1.3-65 mM), N-acetylcysteine (0.6-15 mM), glutathione (1 microM-0.1 mM), glutathione peroxidase (0.1-1 Unit/ml), pentoxifylline (60 microM-36 mM), colchicine (0.025-250 nM) and aurothioglucose (1.15-23 microM) were assessed in the fibroproliferation assay for their ability to block the fibroproliferative effect of platelet-derived growth factor. Dexamethasone and aurothioglucose did not affect PDGF-stimulated fibroproliferation, while pentoxifylline, colchicine, cysteamine and N-acetylcysteine effectively reduced fibroproliferation stimulated by PDGF. The effect of pentoxifylline on PDGF stimulated fibroproliferation was compared to trapidil, theophylline and adenosine to assess mechanism of action. All four methylxanthines effectively inhibited PDGF stimulated fibroproliferation. Pentoxifylline was as effective as trapidil (IC50 = 129 microM and 141 microM, respectively), but pentoxifylline was more potent than theophylline (IC50 = 688 microM) and pentoxifylline was not as potent as adenosine (IC50 = 19 microM) in reducing PDGF-stimulated fibroproliferation.

Acetylcysteine↗

PubMedDate not supplied

Targetted correction of a mutant HPRT gene in mouse embryonic stem cells.

Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.

Animals↗