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Targeted disruption of inducible 6-phosphofructo-2-kinase results in embryonic lethality.

Abstract：

:Inducible 6-phosphofructo-2-kinase (iPFK-2; PFKFB3) produces fructose-2,6-bisphosphate (F2,6BP), which is a potent allosteric activator of 6-phosphofructo-1-kinase (PFK-1), the rate-limiting step in glycolysis. iPFK-2 functions as an activator of anaerobic glycolysis within the hypoxic microenvironment of growing tumors. The early embryo is challenged similarly since the process of vasculogenesis does not begin until after embryonic day 7. We hypothesized that iPFK-2 expression is essential for the survival of the growing embryo. First, we cloned the mouse homolog of iPFK2 and found that it is abundantly expressed in cortical neurons, epithelial cells, and secretory cells of the choroid plexus, pancreas, and adrenal gland of the adult mouse. Using gene targeting, we then disrupted exons 3-7 of the mouse iPFK2 gene, which encode the substrate binding site. No full-term homozygous iPFK-2(-/-) progeny were produced from 11 F7 iPFK-2(+/-) crosses and no homozygous iPFK-2(-/-) embryos were detected after 8 days of embryogenesis.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Chesney J,Telang S,Yalcin A,Clem A,Wallis N,Bucala R

doi

10.1016/j.bbrc.2005.02.193

subject

Has Abstract

pub_date

2005-05-27 00:00:00

pages

139-46

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)00419-5

journal_volume

331

pub_type

杂志文章

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