Characterization of Anoctamin 1 in Zebrafish Gastrointestinal Motility

Anoctamin1 codes for a calcium activated chloride channel. Calcium activated chloride channels have recently been shown to be expressed on interstitial cells of Cajal (ICC) in humans and mice. ICC function as pacemaker cells in gastrointestinal (GI) tract motility. Ano1 is a selective marker for ICC and inhibiting ano1 disrupts coordinated motility patterns in the GI tract. The primary goal of this project is to illustrate the functional role of ano1 in the zebrafish GI tract. Multiple transcripts for Ano1 are reported in zebrafish but the expressed transcripts in the gastrointestinal tract are unknown. It is important to identify the specific transcripts that are expressed because Ano1 function is likely to be altered in different transcripts. The objective of this project is to identify the specific transcripts that are expressed in zebrafish gastrointestinal issues and to determine the functional role for Ano1 in zebrafish gastrointestinal motility. Morpholino antisense oligonucleotides (MO) will be used to reduce or knock down the expression of Ano1 in zebrafish. We anticipate that MO knockdown of Ano1 will result in uncoordinated GI motility patterns leading to delayed gastrointestinal transit. MO knockdown of Ano1 will contribute to a better understanding of the role of ICC in GI motility, and will further develop the zebrafish model system