L. Ramamurthy et al., Targeted disruption of the CP2 gene, a member of the NTF family of transcription factors, J BIOL CHEM, 276(11), 2001, pp. 7836-7842
The NTF-like family of transcription factors have been implicated in develo
pmental regulation in organisms as diverse as Drosophila and man. The two m
ammalian members of this family, CP2 (LBP-1c/LSF) and LBP-1a (NF2d9), are h
ighly related proteins sharing an overall amino acid identity of 72%. CP2,
the best characterized of these factors, is a ubiquitously expressed 66-kDa
protein that binds the regulatory regions of many diverse genes. Consequen
tly, a role for CP2 has been proposed in globin gene expression, T-cell res
ponses to mitogenic stimulation, and several other cellular processes. To e
lucidate the in vivo role of CP2, we have generated mice nullizygous for th
e CP2 allele, These animals were born in a normal Mendelian distribution an
d displayed no defects in growth, behavior, fertility, or development. Spec
ifically, no perturbation of hematopoietic differentiation, globin gene exp
ression, or immunological responses to T- and B-cell mitogenic stimulation
was observed. RNA and protein analysis confirmed that the nullizygous mice
expressed no full-length or truncated version of CP2. Electrophoretic mobil
ity shift assays with nuclear extracts from multiple tissues demonstrated l
oss of CP2 DNA binding activity in the -/- lines. However, a slower migrati
ng complex that was ablated with antiserum to NF2d9, the murine homologue o
f LBP-1a, was observed with these extracts. Furthermore, we demonstrate tha
t recombinant LBP-1a can bind to known CP2 consensus sites and form protein
complexes with previously defined heteromeric partners of CP2. These resul
ts suggest that LBP-1a/NF2d9 may compensate for loss of CP2 expression in v
ivo and that further analysis of the role of the NTF family of proteins req
uires the targeting of the NF2d9 gene.