OBJECTIVETo determine the role of Bmi-1 in the submandibular gland (SMG) of mice.

METHODSSMG of 4-week wild-type (WT) and Bmi-1 null (Bmi-1(-/-)) mice was analyzed on the weight, salivary flow rate, hematoxylin-eosin staining morphological differences and the changes in proliferation and aging by histology, immunohistochemistry and Western blotting.

RESULTSCompared with WT mice, the average static salivary flow rate [WT:(0.21 ± 0.02) µg/min,Bmi-1(-/-): (0.10 ± 0.02) µg/min] (P = 0.001) and the submandibular gland weight [WT: (1.89 ± 0.15) µg], Bmi-1(-/-): [(1.34 ± 0.07)µg] (P = 0.003) of the male Bmi-1(-/-) mice were significantly decreased, the number of gland duct increased, and the granular convoluted duct showed reduced diameter and branches. More senescence-associated β-galactosidase positive cells existed in SMG of Bmi-1(-/-)mice (WT:0.00, Bmi-1(-/-): 0.18 ± 0.02), and Ki-67 immunopositive cells decreased in SMG of Bmi-1(-/-) mice (WT:0.40 ∼ 0.47, Bmi-1(-/-): 0.18 ∼ 0.20) (P = 0.000). The expression of p16 (WT:1.00 ± 0.12, Bmi-1(-/-): 0.00 ± 0.00) (P = 0.003) and p19 (WT:0.97 ± 0.09, Bmi-1(-/-): 5.09 ± 0.21) (P = 0.004) were up-regulated dramatically in SMG of the Bmi-1(-/-) mice.

CONCLUSIONSBmi-1 gene deficiency causes abnormal function of SMG by inducing senescence phenotype of SMG.

Animals ; Immunohistochemistry ; Male ; Mice ; Polycomb Repressive Complex 1 ; biosynthesis ; genetics ; Proto-Oncogene Proteins ; biosynthesis ; genetics ; Submandibular Gland ; growth & development ; metabolism ; Up-Regulation