title: Deletion of ATG5 shows a role of autophagy in salivary homeostatic control.
abstract: Autophagy is a catabolic pathway utilized to maintain a balance among the synthesis, degradation, and recycling of cellular components, thereby playing a role in cell growth, development, and homeostasis. Previous studies revealed that a conditional knockout of essential member(s) of autophagy in a variety of tissues causes changes in structure and function of these tissues. Acinar cell-specific expression of knocked-in Cre recombinase through control of aquaporin 5 (Aqp5) promoter/enhancer (Aqp5-Cre) allows us to specifically inactivate Atg5, a protein necessary for autophagy, in salivary acinar cells of Atg5(f/f);Aqp5-Cre mice. There was no difference in apoptotic or proliferation levels in salivary glands of Atg5/Cre mice from each genotype. However, H&E staining and electron microscopy studies revealed modestly enlarged acinar cells and accumulated secretory granules in salivary glands of Atg5(f/f);Aqp5-Cre mice. Salivary flow rates and amylase contents of Atg5/Cre mice indicated that acinar-specific inactivation of ATG5 did not alter carbachol-evoked saliva and amylase secretion. Conversely, autophagy intersected with salivary morphological and secretory manifestations induced by isoproterenol administration. These results identified a role for autophagy as a homeostasis control in salivary glands. Collectively, Atg5(f/f);Aqp5-Cre mice would be a useful tool to enhance our understanding of autophagy in adaptive responses following targeted head and neck radiation or Sjögren syndrome.
authors.affiliation: Department of Nutritional Sciences, The University of Arizona, Tucson, AZ 85721, USA.
authors.forename: M
authors.initials: M
authors.lastname: Morgan-Bathke
authors.forename: H H
authors.initials: HH
authors.lastname: Lin
authors.forename: A M
authors.initials: AM
authors.lastname: Chibly
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: C-H
authors.initials: CH
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Flodby
authors.forename: Z
authors.initials: Z
authors.lastname: Borok
authors.forename: R
authors.initials: R
authors.lastname: Wu
authors.forename: D
authors.initials: D
authors.lastname: Arnett
authors.forename: R R
authors.initials: RR
authors.lastname: Klein
authors.forename: D K
authors.initials: DK
authors.lastname: Ann
authors.forename: K H
authors.initials: KH
authors.lastname: Limesand
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000201:enzymology; D000375:Aging / Q000502:physiology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D051402:Aquaporin 5 / Q000235:genetics / Q000502:physiology*; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D055879:Gene Knock-In Techniques; D055786:Gene Knockout Techniques; D006706:Homeostasis / Q000187:drug effects; D006984:Hypertrophy; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012463:Saliva / Q000201:enzymology / Q000378:metabolism; D012469:Salivary Glands / Q000166:cytology / Q000201:enzymology / Q000254:growth & development / Q000502:physiology*; D022142:Secretory Vesicles / Q000378:metabolism; D017384:Sequence Deletion; D013312:Stress, Physiological / Q000502:physiology; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: D051402:Aquaporin 5; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D018809:Proliferating Cell Nuclear Antigen; D057149:Ubiquitinated Proteins; C045073:Cre recombinase; D019426:Integrases; D000681:Amylases; D053148:Caspase 3; D007545:Isoproterenol
keywords: animal models; apoptosis; isoproterenol; proliferation; salivary gland