Abstract

Kruppel-like factors (KLFs) are transcription factors involved in differentiation and development. EKLF (or KLF1), KLF2, and KLF4 belong to a subclass of KLFs that are similar in regard to their zinc finger DNA-binding domains. EKLF knockout (KO) mouse embryos die between embryonic day 14.5 (E14.5) and E16.5 due to anemia. KLF2 KO embryos die between E12.5 and E14.5 and exhibit heart failure and hemorrhaging. KLF4 KO mice die perinatally owing to a loss of skin-barrier function. EKLF is expressed in erythroid cells, but KLF2 and KLF4 are expressed in multiple tissues. Our laboratory has analyzed compound mutant embryos for EKLF and KLF2 and for KLF2 and KLF4. The double KO embryos have more severe erythroid and/or cardiovascular defects and die earlier than do single knockouts. This indicates that there are interactions between these pairs of KLF genes during development. The phenotypes of the compound mutants and the possible mechanisms for KLF gene interactions are discussed.

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