| First Author | McKnite A | Year | 2023 |
| Journal | Dev Dyn | Volume | 252 |
| Issue | 6 | Pages | 761-769 |
| PubMed ID | 36825302 | Mgi Jnum | J:337004 |
| Mgi Id | MGI:7493540 | Doi | 10.1002/dvdy.578 |
| Citation | McKnite A, et al. (2023) Lack of evidence that fibrillin1 regulates bone morphogenetic protein 4 activity in kidney or lung. Dev Dyn 252(6):761-769 |
| abstractText | BACKGROUND: The Bone morphogenetic protein 4 (BMP4) precursor protein is cleaved at two sites to generate an active ligand and inactive prodomain. The ligand and prodomain form a noncovalent complex following the first cleavage, but dissociate after the second cleavage. Transient formation of this complex is essential to generate a stable ligand. Fibrillins (FBNs) bind to the prodomains of BMPs, and can regulate the activity of some ligands. Whether FBNs regulate BMP4 activity is unknown. RESULTS: Mice heterozygous for a null allele of Bmp4 showed incompletely penetrant kidney defects and females showed increased mortality between postnatal day 6 and 8. Removal of one copy of Fbn1 did not rescue or enhance kidney defects or lethality. The lungs of Fbn1(+/-) females had enlarged airspaces that were unchanged in Bmp4(+/-) ;Fbn1(+/-) mice. Additionally, removal of one or both alleles of Fbn1 had no effect on steady state levels of BMP4 ligand or on BMP activity in postnatal lungs. CONCLUSIONS: These findings do not support the hypothesis that FBN1 plays a role in promoting BMP4 ligand stability or signaling, nor do they support the alternative hypothesis that FBN1 sequesters BMP4 in a latent form, as is the case for other BMP family members. |
