Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects

Autor: Hojae Choi, Scott E. Fraser, Russell E. Jacobs, Arthur D. Lander, Heather A. Jamniczky, Anne L. Calof, Benedikt Hallgrímsson, Jamie Wikenheiser, Shimako Kawauchi, Martha E. Lopez-Burks, Rosaysela Santos
Přispěvatelé: Lo, Cecilia
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Gene Expression
Cell Cycle Proteins
Penetrance
Haploinsufficiency
Cardiovascular
Medical and Health Sciences
Heart Septal Defects
Atrial
Transgenic
Mice
Risk Factors
2.1 Biological and endogenous factors
Aetiology
Biology (General)
Genetics
Pediatric
Heart development
General Neuroscience
Heart
Biological Sciences
medicine.anatomical_structure
Heart Disease
Organ Specificity
Homeobox Protein Nkx-2.5
Female
Endoderm
General Agricultural and Biological Sciences
Cornelia de Lange Syndrome
Lineage (genetic)
QH301-705.5
1.1 Normal biological development and functioning
Mice
Transgenic
Context (language use)
Germ layer
Biology
General Biochemistry
Genetics and Molecular Biology
Atrial septal defects
Cell Line
03 medical and health sciences
Rare Diseases
Underpinning research
medicine
Animals
Genetic Predisposition to Disease
Genetic Association Studies
General Immunology and Microbiology
Agricultural and Veterinary Sciences
Atrial
Heart Septal Defects
NIPBL
medicine.disease
Stem Cell Research
030104 developmental biology
Congenital Structural Anomalies
Generic health relevance
Transcription Factors
Developmental Biology
Zdroj: PLoS Biology, Vol 14, Iss 9, p e2000197 (2016)
PLoS biology, vol 14, iss 9
Santos, R; Kawauchi, S; Jacobs, RE; Lopez-Burks, ME; Choi, H; Wikenheiser, J; et al.(2016). Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects.. PLoS Biol, 14(9), e2000197. doi: 10.1371/journal.pbio.2000197. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/50w416g5
ISSN: 1545-7885
1544-9173
DOI: 10.1371/journal.pbio.2000197.
Popis: Elucidating the causes of congenital heart defects is made difficult by the complex morphogenesis of the mammalian heart, which takes place early in development, involves contributions from multiple germ layers, and is controlled by many genes. Here, we use a conditional/invertible genetic strategy to identify the cell lineage(s) responsible for the development of heart defects in a Nipbl-deficient mouse model of Cornelia de Lange Syndrome, in which global yet subtle transcriptional dysregulation leads to development of atrial septal defects (ASDs) at high frequency. Using an approach that allows for recombinase-mediated creation or rescue of Nipbl deficiency in different lineages, we uncover complex interactions between the cardiac mesoderm, endoderm, and the rest of the embryo, whereby the risk conferred by genetic abnormality in any one lineage is modified, in a surprisingly non-additive way, by the status of others. We argue that these results are best understood in the context of a model in which the risk of heart defects is associated with the adequacy of early progenitor cell populations relative to the sizes of the structures they must eventually form.
Databáze: OpenAIRE
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