Fuso Pharmaceutical Industries, Ltd.

Other

Osaka University

Masaru Okabe

Masahito Ikawa

Tadashi Kimura

Keiichi Kumasawa

Tsutomu Mimura

Shuji Miyagawa

A lentiviral vector was used to produce non-human animals that express human sFLT1 specifically in the murine placenta, to provide model animals of diseases such as pregnancy-induced hypertension syndrome that are close to the clinical conditions, methods for producing the model animals, methods of screening for candidate compounds as therapeutic agents for diseases such as pregnancy-induced hypertension syndrome by using the model animals, and therapeutic agents for diseases such as pregnancy-induced hypertension syndrome. As a result, the model animals were found to exhibit symptoms that are very close to the clinical conditions in human, which are presentation of hypertension as well as placental insufficiency, intrauterine growth retardation, glomerulosclerosis, and proteinuria during pregnancy, and improvement of those symptoms postpartum. Furthermore, when pravastatin was administered to this model animal, it was found that diseases such as pregnancy-induced hypertension syndrome were improved by the activation of placenta-derived growth factor (PIGF) which antagonizes sFLT1.

Model animal for pregnancy-induced hypertension syndrome, and treatment method therefor

The present inventors discovered that genes could be introduced specifically into trophectodermal cells with high efficiency, by infecting blastocysts with viral vectors carrying an arbitrary polynucleotide, or by using a nucleic acid transfection reagent in blastocysts, from which zona pellucida (extracellular matrix covering preimplantation early embryos to protect them from infection of viruses and the like) is removed. This method has no risk of infecting cells of the inner cell mass, which develops into a fetus in the future, with the introduced polynucleotide because the trophectoderm serves as a barrier. The present invention provides methods for introducing foreign genes into only placenta but not fetus, which enables rescue of genetically mutant animals from embryonic lethality due to placental abnormality and allows their birth. Furthermore, it is possible to analyze expression and effect of genes that regulate placental formation or placental function by using these methods.

Trophectodermal cell-specific gene transfer methods

An object of the present invention is to provide a modified gene for mammals having expression level, in mammalian cells, tissues, organs or bodies, several times as high as that of phage-derived Cre recombinase. To attain the aforementioned object, the present invention provides a modified Cre recombinase gene for mammals consisting of codons frequently used in mammalian cells.

Modified CRE recombinase gene for mammals

A monoclonal or polyclonal antibody having a specific binding property to an antigenic site on the human sperm acrosome, which is produced by a hybridoma obtained by fusion between an antibody-producing mammalian (except human) cell immunized with the antigenic site on the human sperm acrosome and a cell having permanent proliferation potency.

Growing community of inventors

Minoo, Japan

Masaru Okabe