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T McQuinn

Publications and source records attributed to T McQuinn.

4 recordsLinked to original sources
PubMed2000

Conotruncal anomalies in the trisomy 16 mouse: an immunohistochemical analysis with emphasis on the involvement of the neural crest.

The trisomy 16 (Ts16) mouse is generally considered a model for human Down's syndrome (trisomy 21). However, many of the cardiac defects in the Ts16 mouse do not reflect the heart malformations seen in patients suffering from this chromosomal disorder. In this study we describe the conotruncal malformations in mice with trisomy 16. The development of the outflow tract was immunohistochemically studied in serially sectioned hearts from 34 normal and 26 Ts16 mouse embryos ranging from 8.5 to 14.5 embryonic days. Conotruncal malformations observed in the Ts 16 embryos included double outlet right ventricle, persistent truncus arteriosus, Tetralogy of Fallot, and right-sided aortic arch. This spectrum of malformations is remarkably similar to that seen in humans suffering from DiGeorge syndrome (DGS). As perturbation of neural crest development has been proposed in the pathogenesis of DGS we specifically focussed on the fate of neural crest derived cells during outflow tract development of the Ts16 mouse using an antibody that enabled us to trace these cells during development. Severe perturbation of the neural crest-derived cell population was observed in each trisomic specimen. The abnormalities pertained to: 1) the size of the columns of neural crest-derived cells (or prongs); 2) the spatial orientation of these prongs within the mesenchymal tissues of the outflow tract; and 3) the location in which the neural crest cells interact with the myocardium. The latter abnormality appeared to be responsible for ectopic myocardialization found in trisomic embryos. Our observations strongly suggest that abnormal neural crest cell behavior is involved in the pathogenesis of the conotruncal malformations in the Ts16 mouse.

Animals↗
PubMed1996

Activation of the cardiac alpha-actin promoter depends upon serum response factor, Tinman homologue, Nkx-2.5, and intact serum response elements.

A murine cardiac specific homeoboxgene, Nkx-2.5/CSX, a potential Drosophila tinman homologue, may have a fundamental role in cardiac myocyte differentiation. DNA binding targets for Nkx-2.5 were recently shown to represent novel homeodomain binding sequences, some of which resembled serum response elements (SREs); [Chen CY, Schwartz RJ (1995): J Biol Chem 270: 15628-15633]. In this study, Nkx-2.5 facilitated serum response factor (SRF) DNA-binding activity to the multiple SREs found on the cardiac alpha-actin promoter and together stimulated cardiac alpha-actin promoter dependent transcription in 10T1/2 fibroblasts. Analysis of cardiac alpha-actin promoter mutants demonstrated the importance of the multiple upstream SREs and an obligatory requirement for an intact proximal SRE1, for providing high levels of activity in the presence of Nkx-2.5 and SRF coexpression. Transfection assays with mutant SRF species indicated that the C-terminal activation domain and DNA-binding MADS box were necessary for transcriptional activity in the presence of Nkx-2.5. Expression of Nkx-2.5 mutants also demonstrated that the homeodomain alone was insufficient for directing promoter activity in the presence of SRF. The central role of SRF in regulating striated alpha-actin gene activity also was revealed by its embryonic expression restricted primarily to myocardium of the developing heart and the myotomal portion of somites. Thus the function of the cardiac actin promoter SREs appeared to provide binding sites for SRF and Nkx-2.5 to interact and elicit striated muscle specific transcription that was independent of the MyoD family.

Actins↗
PubMed1996

Regulation of SERCA 2 expression by thyroid hormone in cultured chick embryo cardiomyocytes.

We investigated the role of thyroid hormone in the physiological perinatal increase in cardiac sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase) expression. We isolated and cultured the cardiomyocytes in 10(-8) M triiodothyronine (T3) for 48 h and then measured SR Ca(2+)-ATPase mRNA and immunodetectable protein contents as well as SR-dependent 45Ca2+ uptake rate. We also examined the effect of T3 on expression of the same gene in monkey kidney CV-1 cells, which do not express thyroid hormone receptors. T3 increased cardiomyocyte SR Ca2+ pump mRNA content by 289 +/- 35%, and immunodetectable SR Ca2+ pump protein content by 255 +/- 44%, and SR-specific 45Ca2+ uptake rate by 189 +/- 22% (P < 0.01 for each). In contrast, T3 had no significant effect on the total cellular RNA or protein contents in the cardiomyocyte, and there was no effect of T3 on Ca(2+)-ATPase mRNA content in the thyroid hormone receptor-negative CV-1 cells. These data demonstrate that T3 increases expression of the cardiac SR Ca2+ pump, that the effect can be localized to the cardiomyocyte, and that the effect is dependent on thyroid hormone receptors. These data are consistent with pretranslational and possibly transcriptional level effect of thyroid hormone on the cardiac SR Ca2+ pump gene (SERCA 2). The gestation-associated increase in thyroid hormone may be at least partially responsible for the previously demonstrated perinatal increase in cardiac SR Ca2+ pump expression.

Animals↗