Table 1.
Phenotype Summary of Inhibin/Activin Subunit, Receptor, and Binding Protein Transgenic and Knockout Mouse Models
| Knockout/Transgenic Mouse Line | Phenotype | Refs. |
|---|---|---|
| βA-subunit knockout | Defects in eyelid development; lack of whiskers and incisors; cleft palates | 159 |
| Developmental failure of incisor and mandibular molars beyond bud stage; maxillary molars unaffected | 156 | |
| βB-subunit knockout | Failure of eyelid fusion during late embryonic development; in females, impaired reproduction associated with perinatal lethality of offspring and increased gestational time | 157 |
| Open eyes at birth in 40% of offspring, resulting in corneal opacity; completely viable and fertile males and females | 158 | |
| βC-subunit knockout, βE-subunit knockout, and βC/βE-double knockout | Normal | 76 |
| βB-subunit knock-in to the βA-subunit locus | Rescue of craniofacial phenotype from βA-knockout; somatic, testicular, genital, and hair growth grossly affected | 163 |
| α-subunit knockout | Infertility in males and females due to development of gonadal tumors | 239 |
| Elevated levels of activin A and B; development of gonadal tumors followed by cachexia wasting syndrome: hepatocellular necrosis around the central vein, parietal cell depletion and mucosal atrophy in the glandular stomach; anemia; and severe weight loss. If gonadectomized at an early age, wasting syndrome does not develop, but adrenocortical sex steroidogenic tumors develop | 240 | |
| α-subunit transgenic | βA- and βB-subunit level reduction in ovaries; reduction in FSH levels; increase in LH levels; 52% reduction in litter size for females. In males, litter size unaffected but 50% reduction in sperm count | 248 |
| Development of ovarian cysts, polyovular follicles, fewer mature antral follicles and corpora lutea; increased serum T levels; reduced serum estradiol levels; 20–40% reduction in testis size | 249 | |
| Activin receptor type II knockout | Variable hypoplasia of the mandible (micrognathia); cleft palate; eyelid closure defects; absence of incisors; defects in Meckel's cartilage; neonatal fatality; in males, delayed fertility and smaller gonads; infertility in females | 159 |
| Betaglycan knockout | Embryonic lethal at E13.5; proliferative defects in heart and apoptosis in liver | 510 |
| Follistatin knockout | Growth retardation; decreased mass of diaphragm and intercostal muscles; shiny taut skin; skeletal defects of hard plate; 13th pair of ribs; abnormal whisker and tooth development; breathing failure; neonatal fatal | 192 |
| α-subunit and activin receptor type II knockout | Normal in terms of weight loss and stomach and liver histology | 241 |
| Development of activin-secreting gonadal tumors without abnormalities in gastric epithelium; ActRII-dependent signaling pathways in inhibin-deficient mice affects gastric epithelial stem cell proliferation | 511 | |
| Reduction of FSHβ mRNA levels similar in mice with ActRII deficiency, α-subunit deficiency, and combined deficiencies; significant reduction of pituitary FSH levels in ActRII-deficient mice and slight increase in α-deficient mice; reduction of pituitary FSH levels in mice with combined deficiencies compared to those with α-deficiency alone; ActRII-deficiency does not affect GnRH biosynthesis or GnRH-receptor expression | 512 | |
| Follistatin transgene in α-inhibin knockout | Less severe wasting syndrome; lower serum activin levels; prolonged survival | 242 |