Table 1.
Summary of the general and reproductive phenotypes of mouse knockout (KO) models for the BMP ligands, receptors, and signaling SMADs that are expressed in the mouse ovary. N/D, no data
| Ligands | KO | Overall Phenotype | Reproductive Phenotype | Reference |
|---|---|---|---|---|
| Bmp2 | Embryonic Lethal | Malformation of the amnion/chorion | Fewer primordial germ cells | [97] |
| Bmp3 | Viable and Fertile | Increased bone density | None noted | [98] |
| Bmp3b (Gdf10) | Viable and Fertile | Regulates osteoblast differentiation | None noted | [99] |
| Bmp4 (Bmp2b) | Embryonic Lethal | Failure to form mesoderm | No primordial germ cells | [42,100,101] |
| Bmp5 | Embryonic Lethal | Failure to form mesoderm | N/D | [102] |
| Bmp6 (Vgr1) | Subfertile | Regulates osteoblast function | Fewer oocytes ovulated | [35] |
| Bmp7 (Op1) | Perinatal Lethal | Bone, kidney, eye defects | N/D | [103] |
| Bmp15 (Gdf9b) | Subfertile | Reproductive | Fewer oocytes ovulated; cumulus function | [27] |
| Gdf9 | Infertile | Female infertility | Folliculogenesis blocked after primary stage | [104] |
| Receptors | ||||
| Acvr2a | Perinatal Lethal (25%) | Female infertility | FSH suppression | [105] |
| Acvr2b | Perinatal Lethal | Lateral asymmetry; cardiac defects | N/D | [106] |
| Bmpr2 | Embryonic Lethal | Failure to form mesoderm | N/D | [107] |
| Acvr1a (Alk2) | Embryonic Lethal | Failure to form mesoderm | No primordial germ cells | [108,109] |
| Bmpr1a (Alk3) | Embryonic Lethal | Failure to form mesoderm | N/D | [110] |
| Bmpr1b (Alk6) | Infertile | Brachydactyly; retinal defects | Cumulus expansion defect; irregular estrous cycle | [54,111] |
| Smads | ||||
| Smad1 | Embryonic Lethal | Failure to connect to placenta | Fewer primordial germ cells | [112] |
| Smad2 | Embryonic Lethal | Multiple defects including failed gastrulation and mesoderm development | N/D | [113,114] |
| Smad3 | Subfertile | Defective immune response, colorectal tumors, | Defective follicle development | |
| Smad4 | Embryonic Lethal | Defective visceral endoderm | No primordial germ cells | [115,116] |
| Smad5 | Embryonic Lethal | Gut, cardiac, brain defects | Fewer primordial germ cells | [117,118] |
| Smad6 | Postnatal lethality (majority) | Cardiac defects | N/D | [60] |
| Smad7 | Embryonic lethality (partially penetrant) | Reduced body size, immune defects, cardiac development (in null model) | Smaller litter sizes (hypomorphic allele) | [61,119] |
| Smad9 (Smad8) | Viable and Fertile | Defective vascular remodeling | None noted | [78,79] |