Using pronuclear injection TCDM has generated more than 1100 transgenic founder mice from over 190 transgenes. Furthermore, 68 gene targeting has been carried out with germ line transmission. Examples of research articles recently published with GM mouse models generated by TCDM are shown below.
2024
Junnila A, Zhang FP, Martínez Nieto G, Hakkarainen J, Mäkelä JA, Ohlsson C, Sipilä P, Poutanen M. HSD17B1 Compensates for HSD17B3 Deficiency in Fetal Mouse Testis but Not in Adults. Endocrinology. 2024 Apr 29;165(6):bqae056. doi: 10.1210/endocr/bqae056.
Talvi S, Jokinen J, Sipilä K, Rappu P, Zhang FP, Poutanen M, Rantakari P, Heino J. Embigin deficiency leads to delayed embryonic lung development and high neonatal mortality in mice. iScience. 2024 Jan 15;27(2):108914. doi: 10.1016/j.isci.2024.108914. eCollection 2024 Feb 16.
2023
Saarikettu J, Lehmusvaara S, Pesu M, Junttila I, Partanen J, Sipilä P, Poutanen M, Yang J, Haikarainen T, Silvennoinen O. The RNA-binding Protein Snd1/Tudor-SN Regulates Hypoxia-responsive Gene Expression. FASEB Bioadv. 2023 Feb 21;5(5):183-198. doi: 10.1096/fba.2022-00115.
2022
Lehtiniemi T, Bourgery M, Ma L, Ahmedani A, Mäkelä M, Asteljoki J, Olotu O, Laasanen S, Zhang F-P, Tan K, Chousal JN, Burow D, Koskinen S, Laiho A, Elo LL, Chalmel F, Wilkinson MF, Kotaja N. SMG6 localizes to the chromatoid body and shapes the male germ cell transcriptome to drive spermatogenesis. NAR 2022 Nov 11;50(20):11470-11491.
Mätlik K, Garton DR, Montaño-Rodriguez A, Olfat S, Eren F, Casserly L, Damdimopoulos A, Panhelainen A, Porokuokka LL, Kopra JJ, Turconi G, Schweizer N, Bereczki E, Piehl F, Engberg G, Cervenka S, Piepponen TP, Zhang F-P, Sipilä P, Jakobsson J, Sellgren CM, Erhardt S, Andressoo J-O. Elevated endogenous GDNF indices altered dopamine signaling in mice and correlates with clinical severity in schizophrenia. Molecular Psychiatry 2022 Aug;27(8):3247-3261.
Scaravilli M, Koivukoski S, Gillen A, Bouazza A, Ruusuvuori P, Visakorpi T, Latonen L. miR-32 promotes MYC-driven prostate cancer. Oncogenesis. 2022 Mar 1;11(1):11.
2020
Gjorgjieva M, Sobolewski C, Ay AS, Abegg D, Correia de Sousa M, Portius D, Berthou F, Fournier M, Maeder C, Rantakari P, Zhang FP, Poutanen M, Picard D, Montet X, Nef S, Adibekian A, Foti M. Genetic Ablation of MiR-22 Fosters Diet-Induced Obesity and NAFLD Development. J Pers Med. 2020 Oct 14;10(4):170.
Sipilä P, Junnila A, Hakkarainen J, Huhtaniemi R, Mairinoja L, Zhang FP, Strauss L, Ohlsson C, Kotaja N, Huhtaniemi I, Poutanen M. The lack of HSD17B3 in male mice results in disturbed Leydig cell maturation and endocrine imbalance akin to humans with HSD17B3 deficiency. FASEB J. 2020 May;34(5):6111-6128.
2019
Zhang F-P, Malinen M, Mehmood A, Lehtiniemi T, Jääskeläinen T, Korhonen H, Laiho A, Elo L, Ohlsson C, Kotaja N, Poutanen M, Sipilä P, Palvimo J. Lack of androgen receptor SUMOylation results in male infertility due to epididymal dysfunction. Nature Communications 2019 Feb 15;10(1):777
2018
Adam M, Heikelä H, Sobolewski C, Portius D, Mäki-Jouppila J, Mehmood A, Adhikari P, Esposito I, Elo LL, Zhang FP, Ruohonen ST, Strauss L, Foti M, Poutanen M. Hydroxysteroid (17β) dehydrogenase 13 deficiency triggers hepatic steatosis and inflammation in mice. FASEB J. 2018 Jan 31:fj201700914R. doi: 10.1096/fj.201700914R.
Hakkarainen J, Zhang F-P, Cisneros Montalvo S, Nurmio M, Toppari J, Ohlsson C, Kotaja N, Sipilä P, Poutanen M. Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility. FASEB J. 2018 Jan 24:fj201700921R. doi: 10.1096/fj.201700921R.
Hilander T, Zhou XL, Konovalova S, Zhang FP, Euro L, Chilov D, Poutanen M, Chihade J, Wang ED, Tyynismaa H. Editing activity for eliminating mischarged tRNAs is essential in mammalian mitochondria. Nucleic Acids Res. 2018 Jan 25;46(2):849-860.
Jaeschke H, Undeutsch H, Patyra K, Löf C, Eszlinger M, Khalil M, Jännäri M, Makkonen K, Toppari J, Zhang FP, Poutanen M, Paschke R, Kero J. Hyperthyroidism and Papillary Thyroid Carcinoma in Thyrotropin Receptor D633H Mutant Mice. Thyroid. 2018 Oct;28(10):1372-1386.
2017
Ohlsson C, Hammarstedt A, Vandenput L, Saarinen N, Ryberg H, Windahl SH, Farman HH, Jansson JO, Movérare-Skrtic S, Smith U, Zhang FP, Poutanen M, Hedjazifar S, Sjögren K. Increased adipose tissue aromatase activity improves insulin sensitivity and reduces adipose tissue inflammation in male mice. Am J Physiol Endocrinol Metab. 2017 Oct 1;313(4):E450-E462.
Latonen L, Scaravilli M, Gillen A, Hartikainen S, Zhang FP, Ruusuvuori P, Kujala P, Poutanen M, Visakorpi T. In Vivo Expression of miR-32 Induces Proliferation in Prostate Epithelium. Am J Pathol. 2017 Nov;187(11):2546-2557
Heinonen J, Zhang FP, Surmann-Schmitt C, Honkala S, Stock M, Poutanen M, Säämänen AM. Defects in chondrocyte maturation and secondary ossification in mouse knee joint epiphyses due to Snorc deficiency. Osteoarthritis Cartilage. 2017 Jul;25(7):1132-1142. doi: 10.1016/j.joca.2017.03.010.
Da Ros M, Lehtiniemi T, Olotu O, Fischer D, Zhang FP, Vihinen H, Jokitalo E, Sironen A, Toppari J, Kotaja N. FYCO1 and autophagy control the integrity of the haploid male germ cell-specific RNP granules. Autophagy. 2017 Feb;13(2):302-321.
Lehti MS, Zhang FP, Kotaja N, Sironen A. SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation. Development. 2017 Jul 15;144(14):2683-2693.
2016
Tammimäki A, Aonurm-Helm A, Zhang FP, Poutanen M, Duran-Torres G, Garcia-Horsman A, Männisto PT. Generation of membrane-bound catechol-O-methyl transferase deficient mice with disctinct sex dependent behavioral phenotype. J Physiol Pharmacol. 2016 Dec;67(6):827-842.
Koli K, Sutinen E, Rönty M, Rantakari P, Fortino V, Pulkkinen V, Greco D, Sipilä P and Myllärniemi M. Gremlin-1 overexpression in mouse lung reduces silica-induced lymphocyte recruitment – a link to idiopathic pulmonary fibrosis through negative correlation with CXCL10 chemokine. PLoS One 2016 Jul 18;11(7):e0159010. doi: 10.1371/journal.pone.0159010.
Morton NM, Beltram J, Carter RN, Michailidou Z, Gorjanc G, McFadden C, Barrios-Llerena ME, Rodriguez-Cuenca S, Gibbins MT, Aird RE, Moreno-Navarrete JM, Munger SC, Svenson KL, Gastaldello A, Ramage L, Naredo G, Zeyda M, Wang ZV, Howie AF, Saari A, Sipilä P, Stulnig TM, Gudnasson V, Kenyon CJ, Seckl JR, Walker BR, Webster SP, Dunbar DR, Churchill GA, Vidal-Puig A, Fernandez-Real JM, Emilsson V, Horvat S. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness. Nat Med. 2016 Jun 6. doi: 10.1038/nm.4115.
Calo N, Ramadori P, Sobolewski C, Romero Y, Maeder C, Fournier M, Rantakari P, Zhang FP, Poutanen M, Dufour JF, Humar B, Nef S, Foti M. Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption. Gut 2016 Nov;65(11):1871-1881.
Björkgren I, Alvarez L, Blank N, Balbach M, Turunen H, Laajala TD, Toivanen J, Krutskikh A, Wahlberg N, Huhtaniemi I, Poutanen M, Wachten D, Sipilä P. Targeted inactivation of the mouse beta-defensin41 alters sperm flagellar beat pattern and zona pellucida binding. Mol Cell Endocrinol 2016 427:143-54.
Määttä JA, Bendre A, Laanti M, Büki KG, Rantakari P, Tervola P, Saarimäki J, Poutanen M, Härkönen P, Väänänen K. Fam3c modulates osteogenic cell differentiation and affects bone volume and cortical bone mineral density. BoneKey Reports, 5:787, 2016.
2015
Kumar A, Kopra J, Varendi K, Porokuokka LL, Panhelainen A, Kuure S, Marshall P, Karalija N, Härma MA, Vilenius C, Lilleväli K, Tekko T, Mijatovic J, Pulkkinen N, Jakobson M, Jakobson M, Ola R, Palm E, Lindahl M, Strömberg I, Võikar V, Piepponen TP, Saarma M, Andressoo JO. GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function. PLoS Genet. 2015 Dec 17;11(12):e1005710. doi: 10.1371/journal.pgen.1005710.
Sareila O, Hagert C, Rantakari P, Poutanen M, Holmdahl R. Direct Comparison of a Natural Loss-of-Function Single Nucleotide Polymorphism with a Targeted Deletion in the Ncf1 Gene Reveals Different Phenotypes. PLoS One 2015 10(11):e0141974. doi: 10.1371/journal.pone.0141974.
Modi H, Jacovetti C, Tarussio D, Metref S, Madsen O, Zhang FP, Rantakari P, Poutanen M, Nef S, Gorman T, Regazzi R, Thorens B. Autocrine action of IGF2 regulates adult β cell mass and function. Diabetes 2015 64(12):4148-57.
Hakkarainen J, Jokela H, Pakarinen P, Heikelä H, Kätkänaho L, Vandenput L, Ohlsson C, Zhang FP, Poutanen M. Hydroxysteroid (17β)-dehydrogenase 1-deficient female mice present with normal puberty onset but are severely subfertile due to a defect in luteinization and progesterone production. FASEB J 2015 29:3806-16.
2014
Movérare-Skrtic S, Henning P, Liu X, Nagano K, Saito H, Börjesson AE, Sjögren K, Windahl SH, Farman H, Kindlund B, Engdahl C, Koskela A, Zhang FP, Eriksson EE, Zaman F, Hammarstedt A, Isaksson H, Bally M, Kassem A, Lindholm C, Sandberg O, Aspenberg P, Sävendahl L, Feng JQ, Tuckermann J, Tuukkanen J, Poutanen M, Baron R, Lerner UH, Gori F, Ohlsson C. Osteoblast-derived WNT16 represses osteoclastogenesis and prevents cortical bone fragility fractures. Nat Med 20:1279-88, 2014.
Karikoski M, Marttila-Ichihara F, Elima K, Rantakari P, Hollmén M, Kelkka T, Gerke H, Huovinen V, Irjala H, Holmdahl R, Salmi M, Jalkanen S. Clever-1/stabilin-1 controls cancer growth and metastasis. Clin Cancer Res 20:6452-64, 2014.
2013
Strauss L, Rantakari P, Sjögren K, Salminen A, Lauren E, Kallio J, Damdimopoulou P, Boström M, Boström PJ, Pakarinen P, Zhang F, Kujala P, Ohlsson C, Mäkelä S, Poutanen M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens. FASEB J 2013 27:1342-50.
2012
Ventelä S, Come C, Mäkelä J-A, Hobbs RM, Mannermaa L, Kallajoki M, Chan EK, Pandolfi PP, Toppari J and Westermarck J. CIP2A promotes proliferation of spermatogonial progenitor cells and spermatogenesis in mice. PLoS One 2012 7(3):e33209. doi: 10.1371/journal.pone.0033209.
Turunen HT, Sipilä P, Krutskikh A, Toivanen J, Mankonen H, Hämäläinen V, Björkgren I, Huhtaniemi I, Poutanen M. Loss of cysteine-rich secretory protein 4 (Crisp4) leads to deficiency in sperm-zona pellucida interaction in mice. Biol Reprod 2012 16;86(1):1-8.
Turunen HT, Sipilä P, Strauss L, Björkgren I, Huhtaniemi I, Poutanen M. Loss of Bmyc results in increased apoptosis associated with upregulation of Myc expression in juvenile murine testis. Reproduction 2012 144(4):495-503.
Krutskikh A, Poliandri A, Cabrera-Sharp V, Dacheux JL, Poutanen M, Huhtaniemi I. Epididymal protein Rnase10 is required for post-testicular sperm maturation and male fertility. FASEB J. 2012 26(10):4198-209.
2010
Rantakari P, Nikkilä J, Jokela H, Ola R, Pylkäs K, Lagerbohm H, Sainio K, Poutanen M, Winqvist R. Inactivation of Palb2 gene leads to mesoderm differentiation defect and early embryonic lethality in mice. Hum Mol Genet. 2010 19(15):3021-9.
Jokela H, Rantakari P, Lamminen T, Strauss L, Ola R, Mutka AL, Gylling H, Miettinen T, Pakarinen P, Sainio K, Poutanen M. Hydroxysteroid (17beta) dehydrogenase 7 activity is essential for fetal de novo cholesterol synthesis and for neuroectodermal survival and cardiovascular differentiation in early mouse embryos. Endocrinology 2010 151(4):1884-92.
Rantakari P, Lagerbohm H, Kaimainen M, Suomela JP, Strauss L, Sainio K, Pakarinen P, Poutanen M. Hydroxysteroid (17{beta}) dehydrogenase 12 is essential for mouse organogenesis and embryonic survival. Endocrinology 2010 151(4):1893-901.
Rantakari P, Strauss L, Kiviranta R, Lagerbohm H, Paviala J, Holopainen I, Vainio S, Pakarinen P, Poutanen M. Placenta defects and embryonic lethality resulting from disruption of mouse hydroxysteroid (17-beta) dehydrogenase 2 gene. Mol Endocrinol 2008 22(3):665-75.