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A Novel Approach to Identify Genes Related to FGID
Author(s) -
Gombash Sara,
Cowley Christopher,
Fitzgerald Julie,
Iyer Chitra,
McGovern Vicki,
Fried David,
Williams Kent,
Burghes Arthur,
Christofi Fedias,
Gulbransen Brian,
Foust Kevin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1002.16
Subject(s) - nestin , enteric nervous system , biology , myenteric plexus , genetically modified mouse , gene expression , microbiology and biotechnology , transgene , neuroscience , gene , stem cell , immunology , immunohistochemistry , neural stem cell , biochemistry
To investigate novel genes involved in functional gastrointestinal disorders, we disrupted a master regulator of mRNA splicing, the survival motor neuron (SMN) protein. SMN disruption leads to widespread changes in gene expression but has not been evaluated for effects in the gastrointestinal (GI) tract. Mice with a Nestin‐cre transgene were crossed to cre reporter mice to analyze expression in the enteric nervous system (ENS). Gene expression was detected in excitatory and sensory neurons, interneurons, and intraganglionic glia throughout the myenteric plexus but not muscle. Next, nestin‐cre mice were crossed to mice with a floxed Smn allele on a SMNΔ7 background (SMN2 +/+ ;SMNΔ7 +/+ ;Smn F7/‐ ) to produce Nestin‐F7 mice. In organ baths, SMN reduction disrupted colon longitudinal muscle contraction during high frequency electrical field stimulation (EFS). Muscle relaxation was consistently greater in control tissue. The addition of L‐NAME had no effect on differences between control and Nestin‐F7 responses. Tissues showed no morphological changes or cell loss. Gastric emptying and intestinal transit were significantly slower in Nestin‐F7 mice compared to controls. Nestin‐F7 mice had dry, infrequent stool that corresponded to reduced colonic motility in the bead latency test. Collectively, these data suggest that SMN reduction results in impaired GI function. Future studies will identify specific enteric cell types sensitive to SMN reduction and evaluate mRNA expression in those cells.