Vitronectin is not essential for normal mammalian development and fertility.
Vitronectin (VN) is an abundant glycoprotein present in plasma and the extracellular matrix of most tissues. Though the precise function of VN in vivo is unknown, it has been implicated as a participant in diverse biological processes, including cell attachment and spreading, complement activation, and regulation of hemostasis. The major site of synthesis appears to be the liver, though VN is also found in the brain at an early stage of mouse organogenesis, suggesting that it may play an important role in mouse development. Genetic deficiency of VN has not been reported in humans or in other higher organisms. To examine the biologic function of VN within the context of the intact animal, we have established a murine model for VN deficiency through targeted disruption of the murine VN gene. Southern blot analysis of DNA obtained from homozygous null mice demonstrates deletion of all VN coding sequences, and immunological analysis confirms the complete absence of VN protein expression in plasma. However, heterozygous mice carrying one normal and one null VN allele and homozygous null mice completely deficient in VN demonstrate normal development, fertility, and survival. Sera obtained from VN-deficient mice are completely deficient in "serum spreading factor" and plasminogen activator inhibitor 1 binding activities. These observations demonstrate that VN is not essential for cell adhesion and migration during normal mouse development and suggest that its role in these processes may partially overlap with other adhesive matrix components.
Zheng
X
X
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650, USA.
Saunders
T L
TL
Camper
S A
SA
Samuelson
L C
LC
Ginsburg
D
D
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology; D002460:Cell Line; D002678:Chimera; D003433:Crosses, Genetic; D017931:DNA Primers; D005091:Exons; D005260:Female; D005298:Fertility / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D015870:Gene Expression; D015698:Genomic Library; D006200:Hair Color / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012727:Sex Characteristics; D013234:Stem Cells / Q000502:physiology*; D019096:Vitronectin / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*
D017931:DNA Primers; D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin