Fst Conditional Knockout mouse models

Fst, ortholog of human FST, encodes follistatin, a secreted glycoprotein built from an N-terminal domain and three follistatin domains that neutralizes TGF-beta superfamily ligands by wrapping two molecules of activin A in a ring that buries both type I and type II receptor interfaces, an irreversible steric block rather than competitive inhibition. The same architecture binds myostatin encoded by Mstn, GDF11, and several BMPs, and heparan sulfate affinity distinguishes the tissue-retained FST288 isoform from the circulating FST315 form generated by alternative splicing. Nulls die within hours of birth with growth retardation, taut skin, rib and palate defects, so conditional floxed alleles are mandatory for adult muscle, reproductive, or metabolic studies. Isoform-selective knockins are uniquely informative here because retention versus circulation determines whether inhibition is local or systemic, and overexpression or AAV delivery models test muscle hypertrophy directly. The related genes Fstl3 and Inhba-binding partners modulate the same ligand pool, so document them when scoring muscle mass or folliculogenesis endpoints.

Tissue restricted knockout of Fst keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.