The Ad4BP/SF1 Function of Testes BACAd4BPtTAZ Transgenic-Knockout Mice normally regulated during Development.*)

Fatchiyah1,2,3, Mohamad Zubair2, Ken-Ichirou Morohashi2,3

1 Lab. of Molecular & Cellular Biology, Department of Biology, Brawijaya University, Malang 65145, Indonesia, ²Division of Sex Differentiation, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki-Japan 444-8787, ³Department of Molecular Biomechanics, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8585, Japan.

Abstract

To address the function of Ad4BP/SF1 in developing gonad on Ad4BP/SF1 knockout mouse, we have modified the BACAd4BP endogenous by homologous recombinant with modification cassette-containing Tet-Off system and LacZ reporter genes to allow the expression of Ad4BP/SF1 in developing tissues and organ differentiation, regulate of Ad4BP/SF1 mechanism, and reveal the defect due to Ad4BP/SF1 deficiency. The BACAd4BPtTAZ recombinant has a potential to express a lacZ reporter gene and Ad4BP/SF-1 in the tissues where the endogenous Ad4BP/SF-1 gene is expressed. Expectedly, the lacZ expressions in the BAC transgenic mice mostly recapitulated the endogenous gene expressions. However, protein level of upregulated Ad4BP/SF-1 varied among the transgenic mice. Showing a good correlation with the expression levels, the transgene differentially affected the target tissues. We further applied the BAC-transgenic mice to rescue Ad4BP/SF-1 gene disrupted mouse. Interestingly, although the Ad4BP/SF1 protein expression levels are slightly high in testes of BACd4BPtTAZ-Tg mice, the BAC recombinants successfully rescued and normally developed the gonad of the KO mouse.

Keywords: Ad4BP, SF1, BAC transgenic, Steroidogenesis, Testis

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Transgenic and Knockout Mice in Human Disease Research: Novel Insights into Pathophysiology and Perspectives*)

Dra. Fatchiyah, M.Kes. Ph.D.
Brawijaya University, Jl. Veteran, Malang 65145
Email: fatchiya@brawijaya.ac.id

ABSTRACT
The ability to engineer the mouse genome has proven useful for a variety of applications in research, medicine and biotechnology. The development of transgenic and knockout technologies has driven an explosion in new animal models of disease. These engineered diseases are a departure from previous animal models in that pathological syndromes are created from a priori assumptions about how disease pathogenesis could develop. Both of mice models have become powerful reagents for modeling genetic disorders, understanding embryonic development and evaluating therapeutics. These mice and the cell lines derived from them have also accelerated basic research by allowing scientists to assign functions to genes, dissect genetic pathways, and manipulate the cellular or biochemical properties of proteins. Such models have been useful in providing new information on the functions of receptor of the insulin or insulin-like growth factor family have been implicated in the regulation of pancreatic β-cells and insulin secretion. However, the contrived nature of the systems might generate false information, unless validated by careful reference to human disease and spontaneous disease in other animal models.

Keywords: transgenic, knockout mouse model, pathological function

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*)This paper is presented at the International Seminar, “Management Strategy on Animal Health and Production Control in the Anticipation of  Global Warming for the Achievement of Millennium Developmental Goals.” This seminar was hold on June, 3-4^th 2008 at the ELMI Hotel Surabaya, East Java, Indonesia