Disease relevance of Lphn1

• Functionally, IgG1-Lec 2 and IgG1-Lec 8 were comparable to wild type with respect to in vivo half-life, affinity for Fc gammaRI, and capacity for complement-mediated hemolysis [1].
• This was partially purified and proved indistinguishable from the natural toxin with respect to its molecular mass, immunostaining, toxicity to mice, binding to alpha-latrotoxin receptors (latrophilin or neurexin Ialpha) and electrophysiological recording in the mouse diaphragm [2].
• CHOP2 cells, a subline of the Chinese hamster ovary (CHO) cell glycosylation mutant Lec2 which expresses polyoma virus large T antigen, was used as the host cell line to select cDNAs conferring resistance to the toxic effects of ricin [3].

High impact information on Lphn1

• We have extended these studies by producing the same dansyl-specific IgG1 in cell lines deficient in attachment of sialic acid (Lec 2) and galactose (Lec 8) [1].
• While IgG1-Lec 2 was essentially identical to wild type in its capacity to interact with individual components of the classical complement activation pathway, IgG1-Lec 8 demonstrated equivalent maximal binding at lower concentrations and was preferentially bound by mannose-binding protein [1].
• To study O-linked glycosylation, glycophorin A cDNA was transfected into the Lec 2, Lec 8, and ldlD glycosylation-deficient CHO cell lines [4].
• The glycosylation profiles of IgG1-Lec 2 and IgG1-Pro-5 were heterogeneous [5].
• We have now produced mouse-human chimeric IgG1 in wild-type Chinese hamster ovary (CHO) cell lines Pro-5 as well as in the glycosylation mutants Lec 2, Lec 8, and Lec 1 [5].

Biological context of Lphn1

• CHOP2 cells acquiring cDNA that either corrected the Lec2 mutation or created a Lec2/Lec1 phenotype were expected to show a selective growth advantage in ricin-containing medium [3].

References