TY - JOUR AB - Deficiency of the Monocarboxylate Transporter 8 (MCT8) severely impairs thyroid hormone (TH) transport into the brain, disrupting brain development as well as peripheral TH homeostasis. Studies assessing MCT8 expression patterns and tissue-specific pathologies induced by local TH-deficiency are often inconclusive due to unreliable antibody staining and the lack of functional tools to specifically target MCT8-expressing cells. For this purpose, we generated non-inducible Mct8-Cre and tamoxifen-inducible Mct8-CreERT2 mice. Mct8-Cre;Sun1-sfGFP mice demonstrated ubiquitous Sun1-sfGFP expression, due to early recombination driven by Mct8 gene expression at the stage of trophoblast implantation. Tamoxifen injection in 6-week-old Mct8-CreERT2 mice induced reporter expression specifically in Mct8-expressing cells in the brain and peripherally in liver, kidney, and thyroid, without leaky reporter expression in vehicle controls. Using vDISCO tissue clearing and 3D-imaging of GFP-nanobody-boosted mice, we further identified the sublingual salivary gland and the prostate as prominent Mct8-expressing organs. Nuclei from Mct8-expressing cells in the brain could selectively be enriched using fluorescence-activated nuclei sorting on Mct8-CreERT2;Sun1-sfGFP mice and characterized as choroid plexus cells and tanycytes. Our new inducible Mct8-CreERT2 line provides researchers with a tool to reliably mark, enrich, and characterize Mct8-expressing cells and to genetically modify genes specifically in these cells to study thyroid hormone transport and function. AU - Molenaar, A. AU - Mallet, N. AU - Bralo, M. AU - Höher, L. AU - Schriever, S.C. AU - Pathak, E. AU - Bernecker, M. AU - Müller, T.D. AU - Ertürk, A. AU - Cebrian Serrano, A. AU - Pfluger, P.T. C1 - 76154 C2 - 58446 TI - A novel tamoxifen-inducible Mct8-CreERT2 mouse model for targeted studies of Mct8-expressing cells and thyroid hormone transport and function. JO - Transgenic Res. VL - 34 IS - 1 PY - 2025 SN - 0962-8819 ER - TY - JOUR AB - The Hippo signal transduction network regulates transcription through Yap/Taz-Tead1-4 in many tissues including skeletal muscle. Whilst transgenic mice have been generated for many Hippo genes, the resultant skeletal muscle phenotypes were not always characterized. Here, we aimed to phenotype the hindlimb muscles of Hippo gene-mutated Lats1−/−, Mst2−/−, Vgll3−/−, and Vgll4+/− mice. This analysis revealed that Lats1−/− mice have 11% more slow type I fibers than age and sex-matched wild-type controls. Moreover, the mRNA expression of slow Myh7 increased by 50%, and the concentration of type I myosin heavy chain is 80% higher in Lats1−/− mice than in age and sex-matched wild-type controls. Second, to find out whether exercise-related stimuli affect Lats1, we stimulated C2C12 myotubes with the hypertrophy agent clenbuterol or the energy stress agent AICAR. We found that both stimulated Lats1 expression by 1.2 and 1.3 fold respectively. Third, we re-analyzed published datasets and found that Lats1 mRNA in muscle is 63% higher in muscular dystrophy, increases by 17–77% after cardiotoxin-induced muscle injury, by 41–71% in muscles during overload-induced hypertrophy, and by 19–21% after endurance exercise when compared to respective controls. To conclude, Lats1 contributes to the regulation of muscle fiber type proportions, and its expression is regulated by physiological and pathological situations in skeletal muscle. AU - Nezhad, F.Y.* AU - Riermeier, A.* AU - Schönfelder, M.* AU - Becker, L. AU - Hrabě de Angelis, M. AU - Wackerhage, H.* C1 - 63975 C2 - 52024 CY - Van Godewijckstraat 30, 3311 Gz Dordrecht, Netherlands SP - 227-237 TI - Skeletal muscle phenotyping of Hippo gene-mutated mice reveals that Lats1 deletion increases the percentage of type I muscle fibers. JO - Transgenic Res. VL - 31 IS - 2 PB - Springer PY - 2022 SN - 0962-8819 ER - TY - JOUR AU - del Hierro, M.J.* AU - Fernández, J.* AU - Castrillo, M.* AU - Martin-Dorado, I.* AU - Montoliu, L.* AU - Hagn, M. AU - Mammano, F.* AU - Herault, Y.* AU - Brown, S.* AU - Ulfhaake, B.* AU - Demengeot, J.* AU - Parkinson, H.* AU - Ramirez-Solis, R.* AU - Kollias, G.* AU - Sedlacek, R.* AU - Soininen, R.* AU - Ruelicke, T.* AU - Jonkers, J.* AU - Iraqi, F.* AU - Hrabě de Angelis, M. C1 - 48174 C2 - 41087 CY - Dordrecht SP - 228 TI - EMMA: The European Mouse Mutant Archive. JO - Transgenic Res. VL - 25 IS - 2 PB - Springer PY - 2016 SN - 0962-8819 ER - TY - JOUR AB - With the advent of modern developmental biology and molecular genetics, the scientific community has generated thousands of newly genetically altered strains of laboratory mice with the aim of elucidating gene function. To this end, a large group of Institutions which form the International Mouse Phenotyping Consortium is generating and phenotyping a knockout mouse strain for each of the ~20,000 protein-coding genes using the mutant ES cell resource produced by the International Knockout Mouse Consortium. These strains are made available to the research community via public repositories, mostly as cryopreserved sperm or embryos. To ensure the quality of this frozen resource there is a requirement that for each strain the frozen sperm/embryos are proven able to produce viable mutant progeny, before the live animal resource is removed from cages. Given the current requirement to generate live pups to demonstrate their mutant genotype, this quality control check necessitates the use and generation of many animals and requires considerable time, cage space, technical and economic resources. Here, we describe a simple and efficient method of genotyping pre-implantation stage blastocysts with significant ethical and economic advantages especially beneficial for current and future large-scale mouse mutagenesis projects. AU - Scavizzi, F.* AU - Ryder, E.* AU - Newman, S.* AU - Raspa, M.* AU - Gleeson, D.* AU - Wardle-Jones, H.* AU - Montoliu, L.* AU - Fernandez, A.* AU - Dessain, M.-L.* AU - Larrigaldie, V.* AU - Khorshidi, Z.* AU - Voulteenaho, R.* AU - Soininen, R.* AU - André, P.* AU - Jacquot, S.* AU - Hong, Y. AU - Hrabě de Angelis, M. AU - Ramirez-Solis, R.* AU - Doe, B.* C1 - 46401 C2 - 37512 SP - 921-927 TI - Blastocyst genotyping for quality control of mouse mutant archives: An ethical and economical approach. JO - Transgenic Res. VL - 24 IS - 5 PY - 2015 SN - 0962-8819 ER - TY - JOUR AU - Fernández, J.* AU - del Hierro, M.J.* AU - André, P.* AU - Scavizzi, F.* AU - Boersma, A.* AU - Olszanska, O.* AU - Larrigaldie, V.* AU - Guan, M.* AU - Bogani, D.* AU - Marschall, S. AU - Fray, M.* AU - Ayadi, A.* AU - Soininen, R.* AU - Ruelicke, T.* AU - Raspa, M.* AU - Takeo, T.* AU - Nakagata, N.* AU - Montoliu, L.* C1 - 32435 C2 - 35062 SP - 851-852 TI - Efficient shipment of refrigerated mouse embryos across Europe. JO - Transgenic Res. VL - 23 IS - 5 PY - 2014 SN - 0962-8819 ER - TY - JOUR AU - Fernández, J.* AU - Hagn, M. AU - Montoliu, L.* AU - Tocchini-Valentini, G.* AU - Herault, Y.* AU - Brown, S.* AU - Ulfhaake, B.* AU - Demengeot, J.* AU - Parkinson, H.* AU - Ramirez-Solis, R.* AU - Kollias, G.* AU - Sedlacek, R.* AU - Soininen, R.* AU - Ruelicke, T.* AU - Jonkers, J.* AU - Iraqi, F.* AU - Hrabě de Angelis, M. C1 - 32437 C2 - 35060 CY - Dordrecht SP - 851 TI - The INFRAFRONTIER research infrastructure and EMMA: The European mouse mutant archive. JO - Transgenic Res. VL - 23 IS - 5 PB - Springer PY - 2014 SN - 0962-8819 ER - TY - JOUR AU - Hagn, M. AU - Ntziachristos, V. AU - INFRAFRONTIER Consortium (*) C1 - 32438 C2 - 35059 CY - Dordrecht SP - 899 TI - Infrafrontier research infrastructure. JO - Transgenic Res. VL - 23 IS - 5 PB - Springer PY - 2014 SN - 0962-8819 ER - TY - JOUR AU - Kühn, R. AU - Brandl, C. AU - Ortiz, O. AU - Wurst, W. C1 - 32436 C2 - 35061 SP - 870 TI - Generation of targeted deletions in mouse zygotes by pairs of TALENs or SGRNAS/Cas9. JO - Transgenic Res. VL - 23 IS - 5 PY - 2014 SN - 0962-8819 ER - TY - JOUR AU - Ntziachristos, V. C1 - 32439 C2 - 35058 SP - 841-842 TI - The amazing opportunities from integrating optoacoustic and transgenic technology. JO - Transgenic Res. VL - 23 IS - 5 PY - 2014 SN - 0962-8819 ER - TY - JOUR AU - Riedasch, A.* AU - Meyer, A.* AU - Scherb, H. AU - Tolba, R.* AU - Schmidt, J.* AU - Mahabir, E. C1 - 5970 C2 - 27676 SP - 347-348 TI - Influence of the additive Ectoine on the cryopreservation success of murine 2-cell embryos using propylene glycol. JO - Transgenic Res. VL - 19 PB - Springer PY - 2010 SN - 0962-8819 ER - TY - JOUR AB - The aim of this study was to determine the susceptibility of murine embryonic stem (mESCs) to mouse hepatitis virus (MHV-A59) and mouse minute virus (MMVp) and the effect of these viruses on germline transmission (GLT) and the serological status of recipients and pups. When recipients received 10 blastocysts, each injected with 10(0) TCID50 MHV-A59, three out of five recipients and four out of 14 pups from three litters became seropositive. When blastocysts were injected with 10(-5) TCID50 MMVp, all four recipients and 14 pups from four litters remained seronegative. The mESCs replicated MHV-A59 but not MMVp, MHV-A59 being cytolytic for mESCs. Exposure of mESCs to the viruses over four to five passages but not for 6 h affected GLT. Recipients were seropositive for MHV-A59 but not for MMVp when mESCs were cultured with the virus over four or five passages. The data show that GLT is affected by virus-contaminated mESCs. AU - Mahabir, E. AU - Reindl, K. AU - Mysliwietz, J. AU - Needham, J.* AU - Bulian, D. AU - Markoullis, K. AU - Scherb, H. AU - Schmidt, J. C1 - 909 C2 - 25859 SP - 45-57 TI - Impairment of germline transmission after blastocyst injection with murine embryonic stem cells cultured with mouse hepatitis virus and mouse minute virus. JO - Transgenic Res. VL - 18 IS - 1 PB - Springer PY - 2009 SN - 0962-8819 ER - TY - JOUR AB - Murine embryonic stem cells (mESCs) inoculated at passage P13 with the mycoplasma species M. hominis, M. fermentans and M. orale and cultured over 20 passages showed reduced growth rate and viability (P < 0.0001) compared to control mESCs. Spectral karyotypic analysis of mycoplasma-infected mESCs showed a number of non-clonal chromosomal aberrations which increased with the duration of infection. The differentiation status of the infected mESCs was most affected at passage P13+6 where the infection was strongest and 46.3% of the mESCs expressed both POU5F1 and SSEA-1 markers whereas 84.8% of control mESCs expressed both markers. The percentage of germline chimeras from mycoplasma-infected mESCs was examined after blastocyst injection and embryo transfer to suitable recipients at different passages and, compared to the respective control group, was most affected at passage P13+5 (50% vs. 90%; P < 0.07). Further reductions were obtained at the same passage in the percentage of litters born (50% vs. 100%; P < 0.07) and in the percentage of pups born (22% vs. 45%; P < 0.001). Thirty three chimeras (39.8%) obtained from blastocyst injection with mycoplasma-infected mESCs showed reduced body weight (P < 0.0001), nasal discharge, osteoarthropathia, and cachexia. Flow cytometric analysis of plasma from chimeras produced with mycoplasma-infected mESCs revealed statistically significant differences in the proportions of T-cells and increased levels of IgG1 (P < 0.001), IgG2a (P < 0.05) and IgM (P < 0.05), anti-DNA antibodies (P < 0.05) and rheumatoid factor (P < 0.01). The present data indicate that mycoplasma contamination of mESCs affects various cell parameters, germline transmission, and postnatal development of the resulting chimeras. AU - Markoullis, K. AU - Bulian, D. AU - Hölzlwimmer, G. AU - Quintanilla-Martinez, L. AU - Heiliger, K.-J. AU - Zitzelsberger, H. AU - Scherb, H. AU - Mysliwietz, J. AU - Uphoff, C.C.* AU - Drexler, H.G.* AU - Thure, A.* AU - Adler, T. AU - Busch, D.H. AU - Schmidt, J. AU - Mahabir, E. C1 - 3680 C2 - 26533 SP - 71-87 TI - Mycoplasma contamination of murine embryonic stem cells affects cell parameters, germline transmission and chimeric progeny. JO - Transgenic Res. VL - 18 IS - 1 PB - Chapman & Hal PY - 2009 SN - 0962-8819 ER -