A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye.

Abstract

BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential signaling molecule during mammalian kidney and eye development.

Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems

“…While complicated by not being a null mutation, the complex phenotype observed in the Crim1 KST264/KST264 mice is not easily explained by disruption to a single known BMP or TGF-␤, although some aspects are similar to those observed in disruption to members of this superfamily. The reduced lens and microphthalmia observed in Crim1 KST264/KST264 mice are perhaps most similar to those in BMP7 null mice (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) and a conditional knockout of BMPR-1A (Beebe et al, 2004). Similarly, BMP7 null mice display dysplastic kidneys (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) as do Crim1 KST264/KST264 , albeit less severely.…”

“…The reduced lens and microphthalmia observed in Crim1 KST264/KST264 mice are perhaps most similar to those in BMP7 null mice (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) and a conditional knockout of BMPR-1A (Beebe et al, 2004). Similarly, BMP7 null mice display dysplastic kidneys (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) as do Crim1 KST264/KST264 , albeit less severely. Yet the digit syndactyly in Crim1 KST264/KST264 mice could be regarded as the opposite of the polydactyly observed in BMP7 null mice (Dudley et al, 1995;Luo et al, 1995;Jena et al, 1997).…”

“…Similarly, BMP7 null mice display dysplastic kidneys (Dudley et al, 1995;Luo et al, 1995;Karsenty et al, 1996;Jena et al, 1997) as do Crim1 KST264/KST264 , albeit less severely. Yet the digit syndactyly in Crim1 KST264/KST264 mice could be regarded as the opposite of the polydactyly observed in BMP7 null mice (Dudley et al, 1995;Luo et al, 1995;Jena et al, 1997). Despite the difference in phenotypes between Crim1 and BMP7 mutants, Crim1 could still be a physiological partner for this ligand in some tissues and the phenotypic differences may reflect a mode of regulation that is not simply antagonism of TGF-␤ superfamily members.…”

Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys

“…7 Recent studies have provided evidence that BMPs, particularly BMP-7, have a key role in the pathogenesis of various renal diseases including early experimental diabetic 8 or obstructive 9 nephropathy. Among BMP ligands, BMP-7 has pivotal roles during embryogenic renal and eye development, 10 and BMP-7 expression is retained in only a few tissues in adults, most prominently in the kidney. 11 In experimental animal nephropathy, BMP-7 has been known to ameliorate fibrotic changes of renal tissues by antagonizing TGF-b-induced profibrogenic activities.…”

BMP7 dose-dependently stimulates proliferation and cadherin-11 expression via ERK and p38 in a murine metanephric mesenchymal cell line

“…BMP7 deletion results in hypocellular kidneys with few nephrons, apoptosis, and accumulation of loose interstitial mesenchyme similar to the kidneys treated with SB203580 (Dudley et al. 1995). …”