ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2009
KCNJ11 knockout morula re-engineered by stem cell diploid aggregation.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Advances in cardiac ATP-sensitive K+ channelopathies from molecules to populations.Circulation. Arrhythmia and electrophysiology · 2011Article
- Induced pluripotent stem cells: developmental biology to regenerative medicine.Nature reviews. Cardiology · 2010Review
- Human K(ATP) channelopathies: diseases of metabolic homeostasis.Pflugers Archiv : European journal of physiology · 2010Review
- c-MYC independent nuclear reprogramming favors cardiogenic potential of induced pluripotent stem cells.Journal of cardiovascular translational research · 2010Article
- Rescue of developmental defects by blastocyst stem cell injection: towards elucidation of neomorphic corrective pathways.Journal of cardiovascular translational research · 2010Article
- Induced pluripotent stem cells: advances to applications.Stem cells and cloning : advances and applications · 2010Article
- Blastocyst injection of embryonic stem cells: a simple approach to unveil mechanisms of corrections in mouse models of human disease.Stem cell reviews and reports · 2009Review
- Targeted disruption of K(ATP) channels aggravates cardiac toxicity in cocaine abuse.Clinical and translational science · 2009Article
- iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism.Circulation research · 2009Article
- Repair of acute myocardial infarction by human stemness factors induced pluripotent stem cells.Circulation · 2009Article
- Stem cell platforms for regenerative medicine.Clinical and translational science · 2009Article
- Induced pluripotent reprogramming from promiscuous human stemness related factors.Clinical and translational science · 2009Article
- Introduction. The blurred boundary between channels and transporters.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2009Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KCNJ11-encoded Kir6.2 assembles with ATP-binding cassette sulphonylurea receptors to generate ATP-sensitive K+ (KATP) channel complexes. Expressed in tissues with dynamic metabolic flux, these evolutionarily conserved yet structurally and functionally unique heteromultimers serve as high-fidelity rheostats that adjust membrane potential-dependent cell functions to match energetic demand. Genetic defects in channel subunits disrupt the cellular homeostatic response to environmental stress, compromising organ tolerance in the adult. As maladaptation characterizes malignant KATP channelopathies, establishment of platforms to examine progression of KATP channel-dependent adaptive behaviour is warranted. Chimeras provide a powerful tool to assay the contribution of genetic variance to stress intolerance during prenatal or post-natal development. Here, KCNJ11 KATP channel gene knockout<-->wild-type chimeras were engineered through diploid aggregation. Integration of wild-type embryonic stem cells into zona pellucida-denuded morula derived from knockout embryos achieved varying degrees of incorporation of stress-tolerant tissue within the KATP channel-deficient background. Despite the stress-vulnerable phenotype of the knockout, ex vivo derived mosaic blastocysts tolerated intrauterine transfer and implantation, followed by full-term embryonic development in pseudopregnant surrogates to produce live chimeric offspring. The development of adult chimerism from the knockout<-->wild-type mosaic embryo offers thereby a new paradigm to probe the ecogenetic control of the KATP channel-dependent stress response.
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