Nj. Sund et al., Hepatocyte nuclear factor 3 beta (Foxa2) is dispensable for maintaining the differentiated state of the adult hepatocyte, MOL CELL B, 20(14), 2000, pp. 5175-5183
Liver-specific gene expression is controlled by a heterogeneous group of he
patocyte-enriched transcription factors. One of these, the winged-helix tra
nscription factor hepatocyte nuclear factor 3 beta (HNF3 beta or Foxa2) is
essential for multiple stages of embryonic development. Recently, HNF3 beta
has been shown to be an important regulator of other hepatocyte-enriched t
ranscription factors as well as the expression of liver-specific structural
genes. We have addressed the role of HNF3 beta in maintenance of the hepat
ocyte phenotype by inactivation of HNF3 beta in the liver. Remarkably, adul
t mice lacking HNF3 beta expression specifically in hepatocytes are viable,
with histologically normal livers and normal liver function. Moreover, ana
lysis of >8,000 mRNAs by array hybridization revealed that lack of HNF3 bet
a affects the expression of only very few genes. Based on earlier work it a
ppears that HNF3 beta plays a critical role in early liver development; how
ever, our studies demonstrate that HNF3 beta is not required for maintenanc
e of the adult hepatocyte or for normal liver function. This is the first e
xample of such functional dichotomy for a tissue specification transcriptio
n factor.