title: Microfibril-associated glycoprotein 2 (MAGP2) loss of function has pleiotropic effects in vivo.
abstract: Microfibril-associated glycoprotein (MAGP) 1 and 2 are evolutionarily related but structurally divergent proteins that are components of microfibrils of the extracellular matrix. Using mice with a targeted inactivation of Mfap5, the gene for MAGP2 protein, we demonstrate that MAGPs have shared as well as unique functions in vivo. Mfap5(-/-) mice appear grossly normal, are fertile, and have no reduction in life span. Cardiopulmonary development is typical. The animals are normotensive and have vascular compliance comparable with age-matched wild-type mice, which is indicative of normal, functional elastic fibers. Loss of MAGP2 alone does not significantly alter bone mass or architecture, and loss of MAGP2 in tandem with loss of MAGP1 does not exacerbate MAGP1-dependent osteopenia. MAGP2-deficient mice are neutropenic, which contrasts with monocytopenia described in MAGP1-deficient animals. This suggests that MAGP1 and MAGP2 have discrete functions in hematopoiesis. In the cardiovascular system, MAGP1;MAGP2 double knockout mice (Mfap2(-/-);Mfap5(-/-)) show age-dependent aortic dilation. These findings indicate that MAGPs have shared primary functions in maintaining large vessel integrity. In solid phase binding assays, MAGP2 binds active TGFβ1, TGFβ2, and BMP2. Together, these data demonstrate that loss of MAGP2 expression in vivo has pleiotropic effects potentially related to the ability of MAGP2 to regulate growth factors or participate in cell signaling.
authors: From the Department of Cell Biology and Physiology.
authors: Michelle D
authors: MD
authors: Combs
authors: Russell H
authors: RH
authors: Knutsen
authors: Thomas J
authors: TJ
authors: Broekelmann
authors: Holly M
authors: HM
authors: Toennies
authors: Thomas J
authors: TJ
authors: Brett
authors: Chantel A
authors: CA
authors: Miller
authors: Daniel L
authors: DL
authors: Kober
authors: Clarissa S
authors: CS
authors: Craft
authors: Jeffrey J
authors: JJ
authors: Atkinson
authors: J Michael
authors: JM
authors: Shipley
authors: Barbara C
authors: BC
authors: Trask
authors: Robert P
authors: RP
authors: Mecham
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D003285:Contractile Proteins / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000172:deficiency* / Q000378:metabolism*; D018390:Gene Targeting; D058685:Genetic Pleiotropy; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009503:Neutropenia / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D011485:Protein Binding; D000072260:RNA Splicing Factors; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D003285:Contractile Proteins; D016326:Extracellular Matrix Proteins; D050505:Mutant Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C016598:microfibrillar protein
keywords: Bone Morphogenetic Protein (BMP); Elastin; Extracellular Matrix; Hematopoiesis; MAGP; Microfibril; Transforming Growth Factor β (TGFβ)
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