Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors

  title={Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors},
  author={Carlos Lois and Elizabeth J. Hong and Shirley Pease and Eric J. Brown and David Baltimore},
  pages={868 - 872}
Single-cell mouse embryos were infected in vitro with recombinant lentiviral vectors to generate transgenic mice carrying the green fluorescent protein (GFP) gene driven by a ubiquitously expressing promoter. Eighty percent of founder mice carried at least one copy of the transgene, and 90% of these expressed GFP at high levels. Progeny inherited the transgene(s) and displayed green fluorescence. Mice generated using lentiviral vectors with muscle-specific and T lymphocyte–specific promoters… 

Rapid generation of knockdown transgenic mice by silencing lentiviral vectors

Two alternative early embryo transduction protocols are described (removal of zona pellucida and subzonal microinjection) and these methodologies offer the possibility of large-scale generation of knockdown transgenic mice for functional genomic studies and enable the production oftransgenic mice in 7 weeks.

Transgenic embryos and mice produced from low titre lentiviral vectors

It is demonstrated that transgenic animals can be generated from low-titre virus vector preparations further simplifying lentiviral transgenesis.

Efficient transgenesis in farm animals by lentiviral vectors

Tissue‐specific transgene expression was achieved by infecting porcine embryos with lentiviral vectors containing the human keratin K14 promoter (LV‐K14).

Variegation and silencing in a lentiviral-based murine transgenic model

Although this lentiviral-based approach led to high levels of transgenesis and germ line transmission, a wide variation in transgene expression was observed in most first and second generation mouse lines, and transGene expression appeared to be the target of epigenetic regulatory mechanism.

Efficient production of germline transgenic chickens using lentiviral vectors

It is demonstrated that lentiviral vectors can be used to generate transgenic lines with an efficiency in the order of 100‐fold higher than any previously published method, with no detectable silencing of transgene expression between generations.

Germ line transmission and expression of an RNAi cassette in mice generated by a lentiviral vector system

Analysis of mosaicism in founder and first generation mice and the observation of multiple silenced transgenes do not favour the use of LentiLox3.7 lentivirus for transgenesis, but a tissue-dependent knockdown of HNF4γ expression in some mice is achieved.

Efficient transgenic rat production by a lentiviral vector

Lentiviral vectors based transgenesis provides a novel powerful tool for efficient transgenic rat generation allowing this most comprehensively studied species to be more broadly used in physiological genomics research.

Generation of tissue-specific transgenic birds with lentiviral vectors.

  • B. B. ScottC. Lois
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
A simple and effective method for producing transgenic birds that express GFP driven by the human synapsin gene I promoter is described and visualization of individual axons and dendrites of neurons in vivo by intrinsic GFP fluorescence is allowed.



The human ubiquitin C promoter directs high ubiquitous expression of transgenes in mice.

The application of a powerful expression vector using the 5′-flanking region of the human ubiquitin C gene that allows very efficient expression of a given transgene in a broad range of tissues is reported.

In Vivo Gene Delivery and Stable Transduction of Nondividing Cells by a Lentiviral Vector

The ability of HIV-based viral vectors to deliver genes in vivo into nondividing cells could increase the applicability of retroviral vectors in human gene therapy.

De novo methylation and expression of retroviral genomes during mouse embryogenesis

Retrovirus genomes introduced into mouse zygotes by microinjection of cloned DNA, or into morula stage pre-implantation mouse embryos by infection with Moloney murine leukaemia virus (M-MuLV), became

Murine PGK‐1 promoter drives widespread but not uniform expression in transgenic mice

The in situ staining of the β‐galactosidase encoded by the transgene indicated extensive cell‐to‐cell variability in its level of expression, suggesting that the Pgk‐1 promoter is regulated so as to be more active in cells requiring high levels of glycolysis.

Development of a Self-Inactivating Lentivirus Vector

Injection of viruses into the rat brain showed that a SIN vector containing the green fluorescent protein gene under the control of the internal CMV promoter transduced neurons as efficiently as a wild-type vector, indicating that the HIV-1 LTR promoter is transcriptionally active in neurons even in the absence of Tat.

The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses

The pCL system permits the investigator to control the level of gene expression in target cells over a 100-fold range, while maintaining uniformly high titers of virus from transiently transfected producer cells.

Germ line integration and Mendelian transmission of the exogenous Moloney leukemia virus.

  • R. Jaenisch
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1976
Together, both experiments indicate that the exogenous M-MuLV can be converted to an endogenous virus after infection of preimplantation embryos and that M- MuLV integrated into the germ line at one out of two possible integration sites.

The cytomegalovirus enhancer: a pan-active control element in transgenic mice

These elements activated expression in 24 of 28 tissues tested in transgenic mice, and the greatest expression was observed in the heart, kidney, brain, and testis.