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Keywords:

  • Alk2;
  • bone morphogenetic protein;
  • gastrulation;
  • mouse

Abstract

Bone morphogenetic proteins (BMPs) have multiple functions during vertebrate development. Previously, it was shown that BMP type I receptor ALK2 (also known as ACVRI, ActRI, or ActRIA) was important for normal mouse gastrulation by deleting exon 4 or exon 5 of Alk2. Recently, flanking exon 7 by loxP sites generated a conditional allele for Alk2. To assess whether the deletion of exon 7 causes functional null of ALK2, and does not produce a dominant negative form or a partially functional form of ALK2, we performed a comparative analysis between Alk2 homozygous mutant embryos with an exon 5 deletion (Alk2Δ55) and embryos with an exon 7 deletion (Alk2Δ77). Both Alk2Δ55 and Alk2Δ77 mutants showed identical morphological gastrulation defects. Histological examinations and molecular marker analyses revealed identical abnormal gastrulation phenotypes in Alk2Δ55 and Alk2Δ77 mutants. Although Fgf8 was expressed in the primitive streak of Alk2Δ55 and Alk2Δ77 mutants, Brachyury, Wnt3a, and Tbx6 were dramatically downregulated in Alk2Δ55 and Alk2Δ77 mutants. These results indicate that deletion of exon 7 for Alk2 leads to a functionally null mutation in vivo, and Alk2 is crucial for sustaining the proper gastrulation events in early mouse embryogenesis. Developmental Dynamics 236:512–517, 2007. Published 2006 Wiley-Liss, Inc.