Tissue Distribution of Murine Muc19/Smgc Gene Products

Abstract

(ARH) S U M M A R Y The recently identified gene Muc19/Smgc encodes two diverse splice variants, Smgc (submandibular gland protein C) and Muc19 (mucin 19). Muc19 is a member of the large gel-forming mucin family and is an exocrine product of sublingual mucous salivary glands in mice. SMGC is a transiently expressed secretion product of developing rodent submandibular and sublingual glands. Little is known about the expression of Muc19/Smgc gene products in other murine salivary and non-salivary tissues containing the mucous cell phenotype. Muc19 expression was therefore initially assessed by RT-PCR and immunohistochemistry. As a complementary approach, we developed a knockin mouse model, Muc19-EGFP, in which mice express a fusion protein containing the first 69 residues of Muc19 followed by enhanced green fluorescent protein (EGFP) as a marker of Muc19 expression. Results from both approaches are consistent, with preferential Muc19 expression in salivary major and minor mucous glands as well as submucosal glands of the tracheolarynx and bulbourethral glands. Evidence also indicates that individual mucous cells of minor salivary and bulbourethral glands produce another gel-forming mucin in addition to Muc19. We further find tissue expression of full-length Smgc transcripts, which encode for SMGC, and are restricted to neonatal tracheolarynx and all salivary tissues. (J Histochem Cytochem 58:141-156, 2010)

Cloning and Characterization of Human MUC19 Gene

“…This pattern is consistent with the reported Muc19 expression in mouse tissues (14), except that, unlike the mouse panel (14), bulbourethral glands were not present in the human tissue panel. Subsequently, we developed antibodies hMUC19Ab_N1 (against N-terminal region) and hMUC19Ab_C1 (against C-terminal region) to determine protein expression.…”

“…Although both Muc5b and Muc19 were expressed by the minor salivary glands, the major glands (i.e., sublingual and submandibular glands) appear to only express Muc19, but not Muc5b (14). Beyond these two organs, Muc19 was detected in bulbourethral glands (Cowper's glands) in the male reproductive system (14), and MUC19 was detected in lacrimal glands of the ocular system (15). Thus, normal MUC19/Muc19 expression appears to be restricted to the glands of various organ systems.…”

The sld Genetic Defect

“…To detect Muc19 in Western blots, blots (nitrocellulose, 0.2 m; GE Healthcare) were probed overnight at 4°C with rabbit anti-Muc19 (1:20,000). Antibody specificity for Muc19 was recently presented (11). Novex Sharp protein standards were used.…”

“…Muc19 glycoproteins are expressed in mucous cells of sublingual glands, as well as in minor mucous glands (11). Interestingly, minor mucous glands produce one or more additional gel-forming mucins (i.e., Muc5ac and Muc5b), whereas Muc19 is the sole gel-forming mucin of sublingual glands.…”

“…Interestingly, minor mucous glands produce one or more additional gel-forming mucins (i.e., Muc5ac and Muc5b), whereas Muc19 is the sole gel-forming mucin of sublingual glands. Muc19 is also found in bulbourethral glands, the inner ear, and a subset of mucous cells within submucosal glands of the tracheolarynx, but not mucous cells of the gastrointestinal tract (11). Given the role of gel-forming mucins in lubrication and hydration, it is of interest to elucidate mechanisms that control Muc19 expression toward the potential future development of therapies to treat patients suffering with dry mouth caused by destruction of salivary glands during autoimmune disease or radiation treatment for head and neck cancer (12,13).…”