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Moreover, for genes that are expressed in multiple tissues or at multiple stages of development, the use of tissue-specific expression of the Cre recombinase allows gene function to be perturbed in specific cell types and\/or at specific times. However, it is well known that putative tissue-specific promoters often drive unanticipated \u2018off-target\u2019 expression. In our efforts to explore the biology of the male reproductive tract, we unexpectedly found that expression of Cre in the central nervous system resulted in recombination in the epididymis, a tissue where sperm mature for ~1\u20132 weeks following the completion of testicular development. Remarkably, we not only observed reporter expression in the epididymis when Cre expression was driven from neuron-specific transgenes, but also when Cre expression in the brain was induced from an AAV vector carrying a Cre expression construct. A surprisingly wide range of Cre drivers \u2013 including six different neuronal promoters as well as the adipose-specific\n                    <jats:italic>Adipoq<\/jats:italic>\n                    Cre promoter \u2013 exhibited off-target recombination in the epididymis, with a subset of drivers also exhibiting unexpected activity in other tissues such as the reproductive accessory glands. Using a combination of parabiosis and serum transfer experiments, we find evidence supporting the hypothesis that Cre may be trafficked from its cell of origin to the epididymis through the circulatory system. Together, our findings should motivate caution when interpreting conditional alleles, and suggest the exciting possibility of inter-tissue RNA or protein trafficking in modulation of reproductive biology.\n                  <\/jats:p>","DOI":"10.7554\/elife.77733","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T11:15:13Z","timestamp":1678878913000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.77733","source":"Crossref","is-referenced-by-count":6,"title":["Evidence for RNA or protein transport from somatic tissues to the male reproductive tract in mouse"],"prefix":"10.7554","volume":"12","author":[{"given":"Vera","family":"Rinaldi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Messemer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0280a3n32","id-type":"ROR","asserted-by":"publisher"}],"name":"Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center","place":["Boston, United States"]},{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute","place":["Cambridge, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Desevin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyun","family":"Sun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany C","family":"Berry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shweta","family":"Kukreja","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Tapper","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Neurobiology, University of Massachusetts Chan Medical School","place":["Worcester, United States"]},{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School","place":["Worcester, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0066-0485","authenticated-orcid":true,"given":"Amy J","family":"Wagers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0280a3n32","id-type":"ROR","asserted-by":"publisher"}],"name":"Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center","place":["Boston, United States"]},{"id":[{"id":"https:\/\/ror.org\/03vek6s52","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Stem Cell Institute","place":["Cambridge, United States"]},{"name":"Paul F. 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