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

Abstract

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 ofCbs−/− 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 andCbs−/− mice. However, the repression was delayed inCbs−/− mice, causing high postnatal AFP levels, which may relate to transcriptional repression of most plasma proteins originating from liver and the observed hepatic dysfunction.

Keywords

• α-Fetoprotein
• Cystathionine β-synthase
• MALDI-TOF/MS
• Proteomics
• Transcriptional regulation
• 2D DIGE