Bmp2 and Bmp4 genetically interact to support multiple aspects of mouse development including functional heart development.
Bone morphogenetic proteins (BMPs) have multiple roles during embryogenesis. Current data indicate that the dosage of BMPs is tightly regulated for normal development in mice. Since Bmp2 or Bmp4 homozygous mutant mice show early embryonic lethality, we generated compound heterozygous mice for Bmp2 and Bmp4 to explore the impact of lowered dosage of these BMP ligands. Genotyping pups bred between Bmp2 and Bmp4 heterozygous mice revealed that the ratio of adult compound heterozygous mice for Bmp2 and Bmp4 is much lower than expected. During embryogenesis, the compound heterozygous embryos showed several abnormalities, including defects in eye formation, body wall closure defects, and ventricular septal defects (VSD) in the heart. However, the ratio of the compound heterozygous embryos was the same as expected. Caesarean sections at E18.5 revealed that half of the compound heterozygotes died soon after birth, and the majority of the dead individuals exhibited VSD. Survivors were able to grow to adults, but their body weight was significantly lower than control littermates. They demonstrated progressive abnormalities in the heart, eventually showing a branched leaflet in atrioventricular valves. These results suggest that the dosage of both BMP2 and 4 is critical for functional heart formation during embryogenesis and after birth.
Uchimura
Takashi
T
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Komatsu
Yoshihiro
Y
Tanaka
Momo
M
McCann
Kelly L
KL
Mishina
Yuji
Y
D000818:Animals; D000831:Animals, Newborn; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D005124:Eye Abnormalities / Q000196:embryology / Q000235:genetics; D005260:Female; D005838:Genotype; D006321:Heart / Q000196:embryology; D006343:Heart Septal Defects / Q000235:genetics / Q000378:metabolism; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4