2D DIGE proteomic analysis highlights delayed postnatal repression of α-fetoprotein expression in homocystinuria model mice

Cystathionine β-synthase-deficient (Cbs^-/-) mice, an animal model for homocystinuria, exhibit hepatic steatosis and juvenile semilethality via as yet unknown mechanisms. The plasma protein profile of Cbs^-/- mice was investigated by proteomic analysis using two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. We found hyperaccumulation of α-fetoprotein (AFP) and downregulation of most other plasma proteins. AFP was highly expressed in fetal liver, but its expression declined dramatically via transcriptional repression after birth in both wild-type and Cbs^-/- mice. However, the repression was delayed in Cbs^-/- mice, causing high postnatal AFP levels, which may relate to transcriptional repression of most plasma proteins originating from liver and the observed hepatic dysfunction.