{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:41:11Z","timestamp":1784011271940,"version":"3.55.0"},"reference-count":47,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2019]]},"abstract":"There is an increasing trend in studies utilizing cell-specific deletion of genes through conditional gene deletion by CRE recombination. Despite numerous advantages, this strategy also has limitations such as ectopic CRE-expression and germline recombination. Two commonly used gonadotropin-releasing hormone (<i>Gnrh<\/i>)-driven CRE-expressing mice both target GnRH neurons. However, a direct comparison of the cells targeted and their phenotypic outcome have not yet been presented. To compare where recombination takes place, we crossed the <i>Gnrh-cre<\/i> and <i>Lhrh-cre<\/i> lines with the <i>Rosa26-LacZ<\/i> reporter mouse. <i>Lhrh-cre<\/i> allowed recombination of the <i>Rosa26-LacZ<\/i> gene in \u223c700 cells, which is comparable to the GnRH neuronal population. Surprisingly, there were &#x3e; 20 times more LacZ expressing cells in the adult <i>Gnrh-cre<\/i>:<i>Rosa26-LacZ<\/i> than the <i>Lhrh-cre<\/i>:<i>Rosa26-LacZ<\/i> brain. The greatest differences in targeting of the <i>Gnrh-cre<\/i> and <i>Lhrh-cre<\/i> lines were found in the septum, the suprachiasmatic nucleus, and the septohypothalamic area. This difference in cells targeted was present from embryonic day 12. A prior study using the <i>Gnrh-cre<\/i> to delete the transcription factor <i>Otx2<\/i> found fewer GnRH neurons, leading to male and female subfertility. To recapitulate this study, we performed a fertility assay in <i>Otx2:Lhrh-cre<\/i> mice. We confirmed the requirement for <i>Otx2<\/i> in GnRH neuron development, fertility and correct gonadotropin hormone release in <i>Otx2:Lhrh-cre<\/i> males, but the subfertility was more modest than in <i>Otx2:Gnrh-cre<\/i> and absent in female <i>Otx2:Lhrh-cre<\/i>. This suggests that ectopic expression of <i>Gnrh-cre<\/i> contributes to the reproductive phenotype observed. Finally, the <i>Cre<\/i> alleles caused germline recombination of the <i>flox<\/i> allele when transmitted from either parent, generating embryonic lethal knock-out offspring, producing smaller live litters.<\/jats:p>","DOI":"10.1159\/000497791","type":"journal-article","created":{"date-parts":[[2019,2,11]],"date-time":"2019-02-11T22:01:34Z","timestamp":1549922494000},"page":"328-342","source":"Crossref","is-referenced-by-count":15,"title":["Differential CRE Expression in Lhrh-cre and GnRH-cre Alleles and the Impact on Fertility in Otx2-Flox Mice"],"prefix":"10.1159","volume":"108","author":[{"given":"Hanne\u00a0M.","family":"Hoffmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Larder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica\u00a0S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael\u00a0J.","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Trang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke\u00a0M.","family":"Devries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0D.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-0410","authenticated-orcid":false,"given":"Pamela\u00a0L.","family":"Mellon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2019,2,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(03)00399-X"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.05.019"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2186"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.06.011"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.240471297"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/gene.20183"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20226"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4298"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/5007"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0041-15.2015"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2723-15.2016"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.4.8751"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1210\/mend.13.12.0380"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-14-05955.1999"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01760.x"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0156"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1688-10.2011"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1126\/science.3024317"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1126\/science.3097822"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/9781119233275.ch5"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/338161a0"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1415226112"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00505"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2008.01746.x"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.039"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.07.023"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10023"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0271"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1210\/en.2014-1277"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.3791\/58352"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.002485"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.06.026"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.21.2646"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.11334.1"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3492"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2005.05.009"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0216"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2018.05.005"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0262"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.12.008"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1013-0"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1016\/0018-506X(82)90020-4"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90150-2"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1210\/me.2002-0189"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(01)00468-3"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1139"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1159\/000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