M= Mouse; R=Rat; H=Human; Rb=Rabbit; G=goat; B=Bovine, MO=Monkey; P=pig; CT= near C-terminus; NT=near N-terminus; Internal=Middle of protein. EC=extracellular; CP=cytoplasmic domains *
 

KLOTHO (The aging suppresser) Antibodies-General Information

Animal models of human aging which display the characteristic diseases associated with aging provide insight into the cause of such diseases. Recently a transgenic mouse model, called Klotho, with several premature aging phenotypes has been described. The name, Klotho, was given by Kuro-o et al for one of the fates, the Greek goddess who spins the thread of life. They display premature aging phenotypes such as Osteoporosis, age related skin changes, ectopic calcifications, atrophy of genital organs and thymus, emphysema and short life span.

KL protein associated with the Klotho mutation is a 1014 amino acid long peptide. It has a putative signal sequence at its N-terminus and a single transmembrane domain near its C-terminus which is postulated to anchor it to the membrane. The extracellular domain has two internal repeats, KL-1 and KL-2 (fig. 1.) which have 20-40% sequence identity to bacterial b-glucosidase of plants and animals and mammalian lactase glycosylceramidase suggesting a role for Klotho in sphingolipid metabolism. kl gene expression was observed to be tissue specific. Improvement of systemic aging phenotypes in kl/kl mice occurs even when the exogenous expression was limited to some organs, suggesting that KL associated aging is regulated through a humoral signaling pathway. KL has been reported to be localized on the cell surface when expressed on Cho cells.
Human kl cDNA is expected to encode a protein of 1012 amino acids and has 86% homology to mouse kl.

ADI has produced rabbit-anti-Klotho antibodies using a specific peptide sequences. Rabbit anti-KL11 antibodies were raised against a 17 mer peptide near the carboxy terminus (possibly cytoplasmic domain) of the murine KL. It shows strong homology (82%) to the Human KL.The control peptides were used to affinity purify the antibodies. The antibody cross-reactivity of KL antibodies amongst other species is not known. The appropriate control immunogenic peptides are also available to confirm specificity of antibodies. Availability of immunodiagnostic reagents for study of factors responsible for aging will further our understanding of the aging phenomenon and help in cure of aging related diseases.