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Biomedical subjects

G Christoph

Publications and source records attributed to G Christoph.

6 recordsLinked to original sources
PubMed1995

A second generation transgenic mouse model expressing both hemoglobin S (HbS) and HbS-Antilles results in increased phenotypic severity.

We report on a second generation of transgenic mice produced by crossing a transgenic mouse line expressing high levels of human alpha and beta S chains (alpha H beta S [beta MDD]) with a line expressing human alpha and beta S-Antilles (beta SAnt). We hypothesized that mice expressing both hemoglobins (Hbs) would have a more severe phenotype because the reduced oxygen affinity and solubility of the beta S-Antilles might enhance the rate and extent of polymer formation. We obtained mice that expressed both beta S and beta S-Antilles. The doubly transgenic mice that are heterozygous for deletion of mouse beta Major (beta MD) occurred with reduced frequency and those that are homozygous for deletion of mouse beta Major (beta MDD) occurred at a much reduced frequency and suffered early mortality. Human alpha was 58% of all alpha globin for all animals, whereas beta S and beta S-Antilles were 34% and 28% of all beta globins for beta MD mice and 42% and 36% for beta MDD mice. Hematocrit, Hb, and mean corpuscular Hb were normal for all transgenic mice, but reticulocyte levels were higher for the doubly transgenic mice versus alpha H beta S [beta MDD] mice older than 30 days (10.0% +/- 1.0% v 4.3% +/- 0.4%; P < .001, mean +/- SE, n = 20 and n = 10, respectively) and control mice (3.9% +/- 0.4%). Reticulocytosis was more severe in mice less than 30 days old ( > 20% for alpha H beta S beta S-Ant[beta MDD] mice). The median mean corpuscular hemoglobin concentration of doubly transgenic mice was higher than that of alpha H beta S[beta MDD] mice with a variable number of very dense cells. Delay times for polymerization of Hb in red blood cells from alpha H beta S beta S-Ant[beta MDD] mice were shorter than those of alpha H beta S[beta MDD] mice, and there were fewer cells with delay times greater than 100 seconds. Urine-concentrating ability in control mice under ambient conditions is 2,846 +/- 294 mOsm and was reduced 30% to 1,958 +/- 240 mOsm, P < 4 x 10(-8) in all mice expressing both transgenes. We conclude that doubly transgenic mice have a more severe phenotype than either of the two parental lines. These mice may be suitable for validating therapeutic intervention in sickle cell disease.

Anemia, Sickle Cell↗
PubMed1990

The cytomegalovirus enhancer: a pan-active control element in transgenic mice.

In an effort to identify widely active positive regulatory elements, we have examined the action of the cytomegalovirus enhancer-promoter in transgenic mice. These elements activated expression in 24 of 28 tissues tested. The greatest expression was observed in the heart, kidney, brain, and testis. Maximum expression further localized to specific cells within the heart and kidney.

Animals↗
PubMed1989

beta-Amyloid precursor is a PEST protein.

The beta-amyloid peptide is generated by proteolytic processing of a family of beta-amyloid precursor proteins. Here we report that beta-amyloid precursor proteins have a primary structure motif known as a PEST sequence, which is predictive of the class of most protease-sensitive rapidly turning over proteins. Consistent with this, the precursors were extraordinarily susceptible to degradation by the calcium-dependent protease calpain I. The identification of beta-amyloid precursors as PEST sequence-containing proteins has implications for both the normal cellular function of beta-amyloid precursor proteins and the mechanisms regulating their expression and processing.

Amino Acid Sequence↗