Inherited deficiency of the lysosomal hydrolase, glucocerebrosidase (encoded by Gba, glucosidase, beta, acid) underlies the autosomal recessive disorder, Gaucher disease. Excessive glucocerebroside storage may lead to the associated tissue dysfunctions. Affected individuals present with a spectrum of clinical symptoms ranging from hepatosplenomegaly, haematological abnormalities, and bone pain, to severe neurodegeneration and premature death. Homozygous knockouts of Gba in mice are perinatal lethal.
In this targeted allele, exons 9-11 are flanked by loxP sites enabling tissue-directed knockouts of the locus via Cre excision. Incomplete expression of Tie2Cre-recombinase (see Stock No. 004128) in cells of hematopoietic and endothelial origin results in deficiency of glucocerebrosidase in the liver, spleen, bone marrow, and peripheral white cells. Glucocerebroside storage in this model leads to progressive splenomegaly with Gaucher cell infiltration and modest storage in the liver by 26 weeks of age. No animals displayed obvious pathology in the bone marrow by 26 weeks of age, but small numbers of Gaucher cells could be found. No obvious haematological differences were seen in affected animals at 26 weeks of age.
LysMCre (see Stock No. 004781) and EIIaCre (see Stock No. 003724) conditional knockout mice fail to develop any notable pathology in the liver, spleen, and bone marrow by 26 weeks of age.
