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Transgenic Over-Expression of a Motor Protein at High Levels Results in Severe Cardiac Pathology (1999)

James, Jeanne ; Osinska, Hanna ; Hewett, Timothy E. ; [et al.]

Springer

Transgenic research 8 (1999), S. 9-22

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ISSN: 1573-9368

Keywords: transgenesis ; myosin light chain ; gene ; muscle

Source: Springer Online Journal Archives 1860-2000

Topics: Biology

Notes: Abstract Transgenesis has become a useful tool in effecting a complete or partial remodeling of the cardiac contractile apparatus. Although gene dosage effects were initially a concern, recent data showed that the heart is able to accommodate varying levels of transgenic over-expression without detectable ill effects. The present study was designed to test the limits of the transgenic paradigm in terms of the production of a cardiac phenotype due simply to the over-expression of a contractile protein. To this end, eight lines of mice which express an isoform of the essential myosin light chain 1 that is normally found in the adult ventricle (ELC1v) were generated. Overt phenotype was correlated both with the level of expression/protein replacement and copy number of the transgene. Two of the lines showed essentially complete replacement of the atrial isoform (ELC1a) with ELC1v. However, the phenotypes of the two lines differed dramatically. The line with the lower copy number (37 copies), and moderate over-expression (16 fold) showed no overt pathology while a line with very high copy number (94 copies) and extremely high levels of over-expression (27–50 fold) developed a significant atrial hypertrophy, dilation and cardiomyopathy. These data indicate that very high expression levels of a contractile protein can cause a cardiac pathology that is unrelated to its degree of replacement in the sarcomere and the unique role(s) it may assume in motor protein function.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1023/A:1008894507995

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Synthesis of (3R,4R)-3-Amino-4-hydroxyhexahydroazepine, the Chiral Constituent of the Antibiotic Ophiocordin (1993)

Müller, Alexander ; Takyar, Dinesh K. ; Witt, Sandra ; [et al.]

Weinheim : Wiley-Blackwell

Liebigs Annalen 1993 (1993), S. 651-655

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ISSN: 0170-2041

Keywords: 3-Amino-4-hydroxyhexahydroazepine ; Cordyceps ophioglossoides ; Antifungals ; Antibiotics ; Ophiocordin ; Chemistry ; Organic Chemistry

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Chemistry and Pharmacology

Notes: (3R,4R)-3-Amino-4-hydroxyhexahydroazepine (2), the optically active constituent of the antifungal antibiotic ophiocordin (1), was prepared in a multistep synthesis starting from D-serine. The absolute configuration was unambigously assigned by a comparison of the synthesized stereoisomer 2 with its racemate and the chiral moiety of the antibiotic ophiocordin by enantioselective gas chromatography.

Additional Material: 1 Ill.