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Ying Liu, Xinzu Gu; Smad4 is Required for the Normal Development and Maintenance of Mouse Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3709.
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© ARVO (1962-2015); The Authors (2016-present)
Smad4, a key intracellular mediator in TGFβ signaling,plays a critical role in the normal development of many tissues/organs.However, its functional role in the development of lacrimalgland (LG) has never been reported. The aim of this study wasto investigate the role Smad4 may play in the development ofLG by using smad4 conditional knockout (CKO) mice and comparingtheir LG changes with normal control mice.
Smad4 in LG, as well as in the lens, cornea and ectoderm ofthe eyelids, was conditionally inactivated by using the Pax6promoterdriven Cre transgenic mice. Lac Z reporter was usedto visualize the developing LG by Xgal staining and standardhistological approaches were used to reveal morphological alterations.
Our findings showed that inactivation of Smad4 resulted in reductionin size and number of acini in the embryonic LG, and pigmentaccumulation within the LG, although it did not affect the formationof the primary lacrimal bud. After birth, LG from Smad4 mutantmice developed slowly, and pigment was observed starting fromP7 mutant LG. Since then, mutant LG was considerably smallerthan normal, and eventually was replaced by adipose tissue.
These results support the notion that Smad4 is essential forthe normal development and maintenance of the mouse LG. Smad4helps inhibit pigmentation and hyperplasia of adipose tissue.
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