Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gene and F213I Mutation.

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the gene, which produces the glucocerebrosidase (GCase) protein. There are more than 500 mutations reported in , among which L444P (p.Leu444Pro) and F213I (p.Phe213Ile) are the most common in the Chinese population, while the function of F213I mutation remains elusive. This study aims to establish the GD mouse model of partially humanized gene with F213I mutation. GCase activity assays showed that the product of partially humanized gene, in which the mouse exons 5-7 were replace by the corresponding human exons, displayed similar activity with the wild-type mouse , while the F213I mutation in the humanized led to significant decrease in enzyme activity. ES cell targeting was used to establish the mice expressing the partially humanized -F213I. mice did not show obviously abnormal phenotypes, but homozygous mice died within 24 h after birth, whose epidermal stratum corneum were abnormal from the wild-type. The GCase activity in mice greatly decreased. In conclusion, our results showed that the partially humanized GD mouse model with the F213I mutation was developed and homozygous F213I mutation is lethal for newborn mice.