Knockout and knockin of the beta1 exon D define distinct roles for integrin splice variants in heart function and embryonic development.
The beta1D integrin is a recently characterized isoform of the beta1 subunit that is specifically expressed in heart and skeletal muscle. In this study we have assessed the function of the beta1D integrin splice variant in mice by generating, for the first time, Cre-mediated exon-specific knockout and knockin strains for this splice variant. We show that removal of the exon for beta1D leads to a mildly disturbed heart phenotype, whereas replacement of beta1A by beta1D results in embryonic lethality with a plethora of developmental defects, in part caused by the abnormal migration of neuroepithelial cells. Our data demonstrate that the splice variants A and D are not functionally equivalent. We propose that beta1D is less efficient than beta1A in mediating the signaling that regulates cell motility and responses of the cells to mechanical stress.
Baudoin
C
C
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Goumans
M J
MJ
Mummery
C
C
Sonnenberg
A
A
D000818:Animals; D002465:Cell Movement; D005314:Embryonic and Fetal Development; D005091:Exons; D018390:Gene Targeting; D005816:Genetic Complementation Test; D014644:Genetic Variation; D006321:Heart / Q000503:physiopathology*; D006579:Heterozygote; D019426:Integrases / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D012326:RNA Splicing; D012333:RNA, Messenger; D014764:Viral Proteins
D019012:Integrin beta1; D012333:RNA, Messenger; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases