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

• α-Fetoprotein (AFP) is hyperaccumulated in the plasma and liver of juvenile Cbs−/− mice.
• Postnatal repression of Afp transcription is delayed in Cbs−/− mouse liver.
• Expression of other major plasma proteins is downregulated in juvenile Cbs−/− mice.
• Expression of these plasma proteins is transcriptionally regulated in the liver.
• High AFP levels may be associated with hepatic steatosis/osteoporosis in Cbs−/− 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.