Technical development for production of gene-modified laboratory rats.

Transgenic rats have been used as model animals for human diseases and organ transplantation and as animal bioreactors for protein production. In general, transgenic rats are produced by pronuclear microinjection of exogenous DNA. Improvement of post-injection survival has been achieved by micro-vibration of the injection pipette. The promoter region, structural gene, chain length and strand ends of the exogenous DNA are not involved in the production efficiency of transgenic rats. Exogenous DNA prepared at 5 microg/ml seemed to be better integrated than lower and higher concentrations. Intracytoplasmic sperm injection (ICSI) has been successfully achieved in rats using a piezo-driven injection pipette. The ICSI technique has not only been applied to rescue infertile male strains but also to produce transgenic rats. The optimal DNA concentration for the ICSI-tg method (0.1 to 0.5 microg/ml) is lower than that for the conventional pronuclear microinjection. Production efficiency was improved when the membrane structure of the sperm head was partially disrupted by detergent or ultrasonic treatment before exposure to the exogenous DNA solution. For successful production of transgenic rats with a modified endogenous gene, establishment of embryonic stem cell lines or alternatively male germline stem cell lines and technical development of somatic cell nuclear transfer are still necessary for this species.

[1]  Megumi Kato,et al.  Direct comparison between ICSI-mediated DNA transfer and pronuclear DNA microinjection for producing transgenic rats. , 2008, Experimental animals.

[2]  N. Nakatsuji,et al.  Rats produced by interspecies spermatogonial transplantation in mice and in vitro microinsemination , 2006, Proceedings of the National Academy of Sciences.

[3]  S. Moisyadi,et al.  Recombinase-mediated mouse transgenesis by intracytoplasmic sperm injection. , 2005, Theriogenology.

[4]  R. Kaneko,et al.  Factors affecting production of transgenic rats by ICSI‐mediated DNA transfer: Effects of sonication and freeze‐thawing of spermatozoa, rat strains for sperm and oocyte donors, and different constructs of exogenous DNA , 2005, Molecular reproduction and development.

[5]  L. Tesson,et al.  Analysis of human CD59 tissue expression directed by the CMV-IE-1 promoter in transgenic rats , 1996, Transgenic Research.

[6]  R. Kaneko,et al.  Production of transgenic rats by ooplasmic injection of spermatogenic cells exposed to exogenous DNA: A preliminary study , 2004, Molecular reproduction and development.

[7]  George Q. Daley,et al.  Derivation of embryonic germ cells and male gametes from embryonic stem cells , 2004, Nature.

[8]  N. Kasai,et al.  Offspring Derived From Intracytoplasmic Injection of Transgenic Rat sperm , 2002, Transgenic Research.

[9]  R. Takahashi,et al.  Production of transgenic rats using cryopreserved pronuclear‐stage zygotes , 1999, Transgenic Research.

[10]  J. Renard,et al.  Generation of Fertile Cloned Rats by Regulating Oocyte Activation , 2003, Science.

[11]  N. Tsunekawa,et al.  Embryonic stem cells can form germ cells in vitro , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Moisyadi,et al.  Expression of Foreign DNA Is Associated with Paternal Chromosome Degradation in Intracytoplasmic Sperm Injection-Mediated Transgenesis in the Mouse1 , 2003, Biology of reproduction.

[13]  Ayako Ishikawa,et al.  Factors affecting premature chromosome condensation of cumulus cell nuclei injected into rat oocytes. , 2003, The Journal of reproduction and development.

[14]  Yali Chen,et al.  Generation and in Vitro Differentiation of a Spermatogonial Cell Line , 2002, Science.

[15]  Kazumi Ito,et al.  Effect of Ca2+/Mg 2+-free Culture Condition on Spontaneous First Cleavage of Rat Oocytes , 2002 .

[16]  B. N. Day,et al.  Production of α-1,3-Galactosyltransferase Knockout Pigs by Nuclear Transfer Cloning , 2002, Science.

[17]  P. Mombaerts,et al.  Efficient metaphase II transgenesis with different transgene archetypes , 2001, Nature Biotechnology.

[18]  Kazumi Ito,et al.  Strontium-Induced Activation Regimen for Rat Oocytes in Somatic Cell Nuclear Transplantation , 2001 .

[19]  R. Yanagimachi,et al.  Sonication Per Se Is Not as Deleterious to Sperm Chromosomes as Previously Inferred1 , 2000, Biology of reproduction.

[20]  A. Schnieke,et al.  Production of gene-targeted sheep by nuclear transfer from cultured somatic cells , 2000, Nature.

[21]  リュウゾウ ヤナギマチ.  Mammalian transgenesis by intracytoplasmic sperm injection , 1999 .

[22]  L. Frati,et al.  Sperm-mediated gene transfer: production of pigs transgenic for a human regulator of complement activation. , 1997, Transplantation proceedings.

[23]  Kazumi Ito,et al.  Factors Affecting the Producing Efficiency of Transgenic Rats , 1997 .

[24]  R. Yanagimachi,et al.  Fertilization and development of mouse oocytes injected with isolated sperm heads. , 1996, Biology of reproduction.

[25]  M. Hirabayashi,et al.  Functions of milk protein gene 5′ flanking regions on human growth hormone gene , 1994, Molecular reproduction and development.

[26]  S. Hochi,et al.  Secretion of bovine α‐lactalbumin into the milk of transgenic rats , 1992 .

[27]  J. Heideman.  Transgenic rats: a discussion. , 1991, Biotechnology.

[28]  R. Hammer,et al.  Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β 2m: An animal model of HLA-B27-associated human disorders , 1990, Cell.

[29]  D. Ganten,et al.  Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene , 1990, Nature.

[30]  S. Hochi,et al.  Fate of exogenous DNA carried into mouse eggs by spermatozoa. , 1990 .

[31]  S. Hochi,et al.  Successful production of transgenic rats , 1990 .

[32]  R. Palmiter,et al.  No simple solution for making transgenic mice , 1989, Cell.

[33]  M. Lavitrano,et al.  Sperm cells as vectors for introducing foreign DNA into eggs: Genetic transformation of mice , 1989, Cell.

[34]  R. Palmiter,et al.  Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. , 1985, Proceedings of the National Academy of Sciences of the United States of America.