{"doi":"10.1016/j.jcmgh.2020.05.009","title":"The Villin1 Gene Promoter Drives Cre Recombinase Expression in Extraintestinal Tissues","abstract":"Villin, encoded by Vil1, is an actin-binding protein expressed by intestinal, hepatobiliary, and renal tubular epithelial cells.1Maunoury R. et al.Development. 1992; 115: 717-728Crossref PubMed Google Scholar Transgenic mice in which the Vil1 promoter drives Cre recombinase expression are widely used to inactivate genes in the intestinal epithelium. The 4 most commonly used Vil1Cre lines were generated by independent groups using distinct promoter constructs.2el Marjou F. et al.Genesis. 2004; 39: 186-193Crossref PubMed Scopus (718) Google Scholar,3Madison B.B. et al.J Biol Chem. 2002; 277: 33275-33283Crossref PubMed Scopus (559) Google Scholar Although these lines have been well-characterized in the intestine, their extraintestinal Cre activity has not been fully defined or compared. We first studied the Tg(Vil1-cre)997Gum and Tg(Vil1-cre)1000Gum transgenic lines in which a 12.4-kilobase region of the Vil1 promoter drives Cre expression.3Madison B.B. et al.J Biol Chem. 2002; 277: 33275-33283Crossref PubMed Scopus (559) Google Scholar We crossed them with Rosa26-Ai9 reporter mice, in which Cre-mediated excision of a stop cassette leads to expression of fluorescent TdTomato (Supplementary Methods).4Madisen L. et al.Nat Neurosci. 2010; 13: 133-140Crossref PubMed Scopus (3877) Google Scholar Both the Vil1Cre/997 and Vil1Cre/1000 lines exhibited Cre activity in epithelial cells throughout the small intestine and colon, as previously described. Unexpectedly, Cre activity was also evident in specific central nervous system (CNS) nuclei: the anterodorsal thalamic nucleus (important for spatial navigation) and 2 small groups of cholinergic neurons in the medulla (Figure 1). All TdTomato+ cells in these nuclei co-localized with the neuronal marker NeuN, and none expressed the oligodendrocyte marker PLP1 (Figure 1). Consistent with these observations, Vil1 transcripts were reported in a subset of thalamic excitatory neurons at postnatal day 215Zeisel A. et al.Cell. 2018; 174: 999-1014 e22Abstract Full Text Full Text PDF PubMed Scopus (1099) Google Scholar but not in the adult mouse CNS (Allen Mouse Brain Atlas),6Lein E.S. et al.Nature. 2007; 445: 168-176Crossref PubMed Scopus (3690) Google Scholar suggesting at least transient expression in these neurons. The Vil1Cre/997 line also drove patchy Cre-mediated recombination throughout the cerebral cortex (Supplementary Figure 1). In contrast, Vil1Cre/1000 mice had no detectable TdTomato in cells in the cerebral cortex (Figure 1) or spinal cord (Supplementary Figure 1) or within intrinsic and extrinsic nerve fibers innervating the gut (Supplementary Figure 2). Therefore, we focused further characterization on these mice. Vil1Cre/1000 mice exhibited Cre-dependent reporter expression in small areas of the exocrine pancreas, rare epithelial cells within the glandular stomach (consistent with prior studies7Qiao X.T. et al.Gastroenterology. 2007; 133: 1989-1998Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar), and some proximal tubules in the kidney (Supplementary Figures 2 and 3, Table 1). Patchy reporter expression was also detected in oviduct epithelium, but not the uterus, ovary, or testis (Supplementary Figures 3 and 4).Table 1Cre-Dependent Reporter Expression in Tissues From Vil1 Promoter-Driven Transgenic Mouse LinesVil1Cre/1000Vil1Cre/20Vil1CreERT2/23Central nervous system BrainRare neurons–– Spinal cord–––Alimentary tract Tongue––– Esophagus––– Stomach (nonglandular)––– Stomach (glandular)RareExtensive– Small intestineExtensiveExtensivePatchy Large intestineExtensiveExtensivePatchy PancreasScatteredExtensive– Liver–Scattered–Urogenital KidneyScatteredExtensive– Bladder–Extensive– Testis–ScatteredScattered Ovary––– OviductScattered–– Uterus–+/––Other Heart––– Lung––– Spleen–Scattered– Adrenal–––NOTE. – indicates reporter expression was not detected. +/– indicates patchy reporter expression was detected in some, but not all, animals. Open table in a new tab NOTE. – indica","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2020,"id":95327,"datarank":0.5416376868966337,"base_score":3.6109179126442243,"endowment":3.6109179126442243,"self_citation_contribution":0.5416376868966337,"citation_network_contribution":0.0,"self_endowment_contribution":0.5416376868966337,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":473655,"name":"Daniella Rastelli","orcid":"0000-0002-9631-3401","position":1,"is_corresponding":false},{"id":250827,"name":"Wei‐Ting Kuo","orcid":"0000-0002-1230-0014","position":2,"is_corresponding":false},{"id":474374,"name":"Jason A. Estep","orcid":null,"position":3,"is_corresponding":false},{"id":473656,"name":"Alexandra Louis","orcid":"0000-0001-7032-5650","position":4,"is_corresponding":false},{"id":473657,"name":"Martin M. Riccomagno","orcid":"0000-0002-1867-4439","position":5,"is_corresponding":false},{"id":250828,"name":"Jerrold R. Turner","orcid":"0000-0003-0627-9455","position":6,"is_corresponding":false},{"id":473658,"name":"Meenakshi Rao","orcid":"0000-0002-8194-9204","position":7,"is_corresponding":false},{"id":473654,"name":"Michael Rutlin","orcid":"0009-0003-3657-1008","position":0,"is_corresponding":true}],"reference_count":11,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32464312","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}