Knockout mouse model developed against ß1,4-galactosyltransferase (GalTase) for the study of diseases in which GalT residues are thought to be critical such as galactosemia and rheumatoid arthritis.
Despite much attention, the function of oligosaccharide chains on glycoproteins and glycolipids remains largely unknown. Our understanding of oligosaccharide function in vivo has been limited to the use of reagents and targeted mutations that eliminate entire classes of oligosaccharide chains. However, most biological functions for oligosaccharides have been attributed to specific terminal sequences on these glycoside chains; yet, there have been few studies that examine the consequences of modifying terminal oligosaccharide structures in vivo.
To address this issue, mice were created bearing a targeted mutation in ß1,4-galactosyltransferase (GalTase), an enzyme responsible for elaboration of many of the proposed biologically active carbohydrate epitopes. Most GalTase-null mice die within the first few weeks after birth and were characterized by stunted growth, thin skin, sparse hair, and dehydration. In addition, spermatogenesis was delayed, the lungs were poorly developed, and the adrenal cortices were poorly stratified. The few surviving adults had puffy skin (myxedema) and difficulty delivering pups at birth (dystocia) and failed to lactate (agalactosis). These defects show that the elimination of GalTase activity leads to polyglandular endocrine insufficiency.
Publication: Developmental Biology. 15 January 1997, Vol. 181(2); 257-267