Gba1^tm2Rlp

A leucine to proline substitution mutation at amino acid position 462 (444 in mature protein) (p.L462P), along with an alanine to proline substitution at position 474 (456 in mature protein) (p.A474P), is associated with Gaucher disease type 2 in humans. The same mutations were introduced in mice using a single insertion mutagenesis procedure, changing leucine codon 462 (TTG) to proline (CCG) and alanine codon 474 (GCA) to proline (CCA). The level of gene expression in brain of mutant mice is similar to wild-type as determined by Northern blot analysis, but enzyme assays with liver, brain, and skin extracts demonstrate that enzyme activity is 4-9% that of wild-type. (J:46243)