Requirement of LIM domains for LIM1 function in mouse head development

Lim1, also known as Lhx1, encodes a LIM homeodomain transcription factor that is essential for head development in the mouse. As with other LIM homeodomain proteins, LIM1 has two LIM domains located N-terminal to the homeodomain, with each LIM domain containing two zinc finger motifs. LIM domains can physically interact with other proteins to form protein complexes that regulate transcription. Previous studies have suggested that LIM domains negatively regulate the transcriptional activity of their associated homeodomains. To investigate the requirement of LIM domains for LIM1 activity, we have mutated the Lim1 gene to alter the conserved amino acid residues that are required for zinc finger structure within both of the LIM domains. Although mice homozygous for this Lim1 allele express the mutant mRNA and protein appropriately, they are a phenocopy for Lim1-null mice. These results suggest that the integrity of the LIM domains is essential for LIM1 activity in mouse head development. genesis 27:12-21, 2000.