Lmna^tm1Otin

The mutation responsible for human Hutchinson-Gilford progeria syndrome, a C to T transition, was introduced 6 nucleotides downstream from the progerin 5' splice site in exon 11 at nucleotide 1824. This mutation does not result in a protein sequence change because both encode a glycine at amino acid position 609 (Gly609Gly). In addition, a neomycin resistance gene flanked by two loxP sites was inserted into intron 10. The C to T mutation activates a cryptic splicing donor site that leads to the accumulation of a truncated form of prelamin A, called progerin. However, the presence of the neo cassette upstream of the mutation prevents the formation of the prelamin A transcripts by blocking this lamin A-specific spicing. This allele is only able to produce the lamin C splice variant. (J:177632)