title: Necessity of Smad4 for the normal development of the mouse lacrimal gland.
abstract: OBJECTIVE
  Smad4, a key intracellular mediator in TGF-β signaling, plays a critical role in the normal development of many tissues/organs. However, its functional role in the development of the lacrimal gland (LG) has never been reported. The aim of this study was to investigate the role Smad4 may play in the development of LG by using Smad4 conditional knockout mice and comparing their LG changes with the LG in normal control mice.
  
  
  METHODS
  Smad4 in the LG, as well as in the lens, cornea, and ectoderm of the eyelids, was conditionally inactivated by using Pax6 promoter-driven Cre-transgenic mice. Lac Z reporter was used to visualize the developing LG by X-gal staining, and standard histologic approaches were used to reveal morphologic alterations.
  
  
  RESULTS
  Inactivation of Smad4 resulted in reduction in the size and number of acini in the embryonic LG and in pigment accumulation within the LG, although it did not affect the formation of the primary lacrimal bud. After birth, the LG from Smad4-mutant mice developed slowly, and pigment was observed starting from the P7 mutant LG. Thereafter, the mutant LG was considerably smaller than the normal LG and was eventually replaced by adipose tissue.
  
  
  CONCLUSIONS
  These results support the notion that Smad4 is essential for the normal development and maintenance of the mouse LG.
authors: Aier Eye Hospital of Changsha, 388, 3rd Segment of Furong Middle Road, Changsha, 410015, Hunan, China, liuying_usc@hotmail.com.
authors: Ying
authors: Y
authors: Liu
authors: Ding
authors: D
authors: Lin
mesh_terms: D000818:Animals; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007765:Lacrimal Apparatus / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000502:physiology; D051901:Smad4 Protein / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D001616:beta-Galactosidase