The submandibular gland (SMG) has been regarded as an age-stable organ in spite of reports on its structural changes with aging. Although the
klotho gene is involved in aging, little information is available regarding its effects on morphological changes of SMGs. The present study examined the histological and immunohistochemical features of SMGs in
klotho-deficient mice - which are well-established aging models - by immunohistochemical and histochemical techniques. Five kinds of cellular markers - against NGF, EGF, Mnand Cu/Zn-SOD, and RITC-conjugated phalloidin - were used for the identification of cell types. In
klotho-deficient mice, the SMGs lost their granular ducts and each lobe diminished. The granular duct showed strong immunoreactivities for NGF and EGF in the wild-type mice, but the NGF- and EGF-immunopositive ducts decreased in number remarkably in
klotho-deficient mice. Interestingly, instead of a loss of the granular duct, the striated duct located on the distal portion in the homozygous mice came to show NGF- and EGF-immunoreactions. Neither Mn- and Cu/Zn-SOD immunoreactivities in the duct system nor the phalloidin- reaction in the myoepithelial cells differed between the wild-type and
klotho-deficient mice. Our findings suggest that the
klotho gene inhibited the differentiation of the granular duct from the striated duct due to the repression and/or down-regulation of sexual and growth hormones.
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