The calcium-activated chloride channel ANOl regulates gastrointestinal motility, mammary growth and sperm physiology
- Author(s): Pardo, David M.
- Advisor(s): Rock, Jason R
- et al.
ANO1 was recently shown to be a critical component of the calcium-activated chloride conductance that regulates numerous physiological processes including epithelial secretion, smooth muscle contraction and tumor growth. Previous studies have also suggested that chloride currents regulate mammary branching morphogenesis and sperm activation during fertilization. However, the premature mortality of Ano1n/n mice has hindered characterization of the diverse roles of ANO1 in adult mouse physiology. In the current studies, Ano1f/f mice were used in combination with two different Cre recombinase alleles (c-KitCreERT 2 and MMTV-Cre) to specifically disrupt ANO1 expression in adult gastrointestinal tissues and mammary gland. The results show that ANO1-mediated slow waves regulate gastrointestinal motility in adult mice and loss of ANO1 delays mammary development during puberty. We also show that ANO1 promotes MMTV-PyMT mammary tumor growth in vitro and in vivo. Finally, using Ano1n/+ mice we demonstrate a novel role for ANO1 in the regulation of sperm capacitation and fertilization in vitro and in vivo.