Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability.
Summary of "Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability."
Loss-of-function analysis of the basic helix-loop-helix (bHLH) transcription factor Hand1 indicates critical roles in development. In an effort to generate a Hand1 cDNA knock-in reporter mouse, we generated two hypomorphic alleles, which extend embryonic survival to between embryonic day (E) 10.5 and E12.5. Heart morphogenesis appears largely normal; however, hypomorphic mice display thin left ventricular myocardium and reduction in pharyngeal mesoderm. Caudal defects, large allantois, and thickened yolk sac are observed and consistent with systemic Hand1 gene deletion. Hand1 mRNA is expressed at 30% of wild-type littermates and known Hand1-dependent genes show intermediate expression compared with wild-type and Hand1 null mice. Interestingly, putative bHLH partners, Hand2 and Twist1, show altered expression in both Hand1 null and hypomorphic backgrounds and intercrossing the Hand1 hypomorphic mice onto the Hand2 systemic null background exacerbates the cardiac and lateral mesoderm phenotypes. Together, these data define a critical threshold of Hand1 expression that is necessary for embryonic survival. Developmental Dynamics, 2010. (c) 2010 Wiley-Liss, Inc.
Affiliation
Riley Heart Research Center, Herman B. Wells Center for Pediatric Research Division of Pediatrics Cardiology, Departments of Anatomy and Medical and Molecular Genetics, Indiana Medical School, Indianapolis, Indiana.
Journal Details
This article was published in the following journal.
Name: Developmental dynamics : an official publication of the American Association of Anatomists
ISSN: 1097-0177
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20737509
- DOI: http://dx.doi.org/10.1002/dvdy.22402
Medical and Biotech [MESH] Definitions
Gene Conversion
The asymmetrical segregation of genes during replication which leads to the production of non-reciprocal recombinant strands and the apparent conversion of one allele into another. Thus, e.g., the meiotic products of an Aa individual may be AAAa or aaaA instead of AAaa, i.e., the A allele has been converted into the a allele or vice versa.
Hemizygote
An individual having only one allele at a given locus because of the loss of the other allele through a mutation (e.g., CHROMOSOME DELETION).
Genetic Association Studies
The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.
Differential Threshold
The smallest difference which can be discriminated between two stimuli or one which is barely above the threshold.
Spectroscopy, Electron Energy-loss
A technique for analysis of the chemical composition of molecules. A substance is bombarded with monochromatic ELECTRONS. Some of the electrons passing through the specimen will lose energy when they ionize inner shell electrons of the atoms in the specimen. The energy loss is element dependent. Analysis of the energy loss spectrum reveals the elemental composition of a specimen. ENERGY-FILTERED TRANSMISSION ELECTRON MICROSCOPY is a type of electron energy loss spectroscopy carried out in electron microscopes specially outfitted to analyze the spectrum of electron energy loss.
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