Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability

Beth A. Firulli, David P. McConville, James S. Byers, Joshua W. Vincentz, Ralston M. Barnes, Anthony B. Firulli

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2748-2760
Number of pages13
JournalDevelopmental Dynamics
Volume239
Issue number10
DOIs
StatePublished - Oct 1 2010

Keywords

  • Extraembryonic mesoderm
  • Hand1
  • Hand2
  • Heart development
  • Ventricle

ASJC Scopus subject areas

  • Developmental Biology
  • Medicine(all)

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    Firulli, B. A., McConville, D. P., Byers, J. S., Vincentz, J. W., Barnes, R. M., & Firulli, A. B. (2010). Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability. Developmental Dynamics, 239(10), 2748-2760. https://doi.org/10.1002/dvdy.22402