α-Klotho mice demonstrate increased expression of the non-sulfated N-glycan form of the HNK-1 glyco-epitope in kidney tissue

The α-Klotho mouse is an animal model that prematurely exhibits phenotypes resembling human aging owing to mutation of the α-Klotho gene. Although α-Klotho mice appear normal at birth, they begin showing multiple age-associated disorders after 3-4 weeks. Meanwhile, overexpression of α-Klotho extends lifespan. Therefore, α-Klotho may be involved in the aging process. The α-Klotho protein has homology to β-glucosidase and is proposed to have glycosidase activity. However, it is unclear whether glycan alterations are present in α-Klotho mice. Here we found increased levels of the non-sulfated HNK-1 glyco-epitope in the kidneys of α-Klotho mice. This phenomenon was also observed in normal aged mice. Immunohistochemical analysis demonstrated that increased non-sulfated HNK-1 glyco-epitope appeared predominantly in the outer half of the renal cortex, where α-Klotho protein is highly expressed. To clarify the cause, the expression of glucuronyltransferase S (GlcAT-S) and the activity of β-glucuronidase were also examined. The expressions of GlcAT-S were comparable in α-Klotho mice and wild-type mice, but β-glucuronidase activity was lower in α-Klotho mice than in wild-type. These results suggest that increased non-sulfated HNK-1 epitope levels in α-Klotho mice may be due to decreased β-glucuronidase activity. Taken together, α-Klotho expression was associated with expression of the non-sulfated HNK-1 epitope.