Cardiovascular and craniofacial defects in Crk-null mice.
The Crk adaptor protein, which is encoded by two splice variants termed CrkI and CrkII, contains both SH2 and SH3 domains but no catalytic region. It is thought to function in signal transduction processes involved in growth regulation, cell transformation, cell migration, and cell adhesion. Although the function of Crk has been studied in considerable detail in cell culture, its biological role in vivo is still unclear, and no Crk-knockout mouse model has been available. Therefore, we generated a complete null allele of Crk in mice by using the Cre-loxP recombination approach. The majority of Crk-null mice die at late stages of embryonic development, and the remainder succumb shortly after birth. Embryos lacking both CrkI and CrkII exhibited edema, hemorrhage, and cardiac defects. Immunohistochemical examination suggested that defects in vascular smooth muscle caused dilation and rupturing of blood vessels. Problems in nasal development and cleft palate were also observed. These data indicate that Crk is involved in cardiac and craniofacial development and that it plays an essential role in maintaining vascular integrity during embryonic development.
Park
Tae-Ju
TJ
St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Boyd
Kelli
K
Curran
Tom
T
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D001808:Blood Vessels / Q000002:abnormalities; D018376:Cardiovascular Abnormalities / Q000196:embryology / Q000235:genetics*; D002972:Cleft Palate / Q000196:embryology / Q000473:pathology*; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000166:cytology / Q000196:embryology / Q000473:pathology; D005260:Female; D018390:Gene Targeting; D005838:Genotype; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D009666:Nose / Q000196:embryology; D010641:Phenotype; D050737:Proto-Oncogene Proteins c-crk / Q000172:deficiency*
D018952:Antigens, CD34; D050737:Proto-Oncogene Proteins c-crk