Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice.
Platelet-derived growth factor, a major mitogen and chemoattractant for a number of cell types, is implicated in the processes of wound healing, tumorigenesis, and differentiation and is recognized by two receptors, alpha and beta. To begin understanding the role of these receptors in development, beta-receptor-deficient mice were generated by gene targeting in ES cells. Mutant mice are hemorrhagic, thrombocytopenic, and severely anemic, exhibit a defect in kidney glomeruli because of a lack of mesangial cells, and die at or shortly before birth. However, many cell types and tissues that express the receptor, including major blood vessels and the heart, appear normal in the absence of the receptor. These results indicate that whereas the beta receptor is essential in certain cell types during embryonic development, its broader role may be masked because of compensation by the alpha-subunit.
Program in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
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Soriano
D000740:Anemia / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006402:Hematologic Diseases / Q000235:genetics*; D006461:Hemolysis / Q000235:genetics; D006470:Hemorrhage / Q000235:genetics; D006720:Homozygote; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics* / Q000502:physiology; D015183:Restriction Mapping; D013921:Thrombocytopenia / Q000235:genetics
D018076:DNA, Complementary; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor