of the Max - MDC

Structure of the Group
Group Leader
Dr. Zsuzsanna Izsvák
Scientists
Dr. Lajos Mátés
Graduate Students
Andrea Schmitt
Diana Pryputniewicz
Yongming Wang
David Grzela
Anantharam Deveraj
Technical Assistant
Janine Fröchlich
Secretariat
Kornelia Dokup
approaches integration rates of viral vectors opening new
avenues for gene therapeutic approaches (INTHER-FP6 coordination)
as well as for genome manipulation techniques in
vivo.
Transposon mutagenesis in rat spermatogonial
stem cells
Lajos Mátés, Janine Fröchlich
Transposons can be harnessed as vehicles for introducing
genetic mutations into genomes. The genes inactivated by
transposon insertion are “tagged” by the transposable element,
which can be used for subsequent cloning of the
mutated allele. The SB system is active in all vertebrates,
including rats. While embryonic stem cell technology is not
established in the rat, the technology of maintaining and
expanding spermatogonial stem cells became available.
Thus, we have extended the utilization of the SB tranposon
to rats, with the goal of knocking out genes implicated in
disease development by transposon mutagenesis in vivo.
The project has enormous potential to develop powerful
genomic tools for rat that is the preferred model organism
of cardiovascular, behavioral studies.
Deciphering the genetic background of hormone
induced breast cancer
Andrea Schmitt
The SB transposon is suitable for somatic mutagenesis and
emerged as a new tool in cancer research an alternative to
retroviral mutagenesis. Transposon based insertional mutagenesis
screen is able to identifiy both oncogenes and
tumor-suppressor genes that normally protect against cancer.
My laboratory is engaged in a project using a rat model
to study the genetics of the estrogen-induced mammary
cancer. Unlike the situation in mouse, the development of
mammary cancer is similar to human as it is also estrogendependent.
The susceptibility to estrogen-induced mammary
cancer behaves as a complex trait controlled by a QTL and
multiple gene-gene interactions. The transposon mutagenesis
approach is expected to be a powerful tool to decipher
the regulatory network.
Knock-outs in the rat: Transposon-mediated insertional mutagenesis
in spermatogonial stem cells
Selected Publications
Kaufman, CD, Izsvák, Z, Katzer, A, Ivics, Z. (2005). Frog Prince
transposon-based RNAi vectors mediate efficient gene knockdown
in human cells. Journal of RNAi and Gene Silencing 1,
97-104.
Walisko, O, Izsvák, Z, Szabó, K, Kaufman, CD, Herold, S, Ivics, Z.
(2006). Sleeping Beauty transposase modulates cell-cycle progression
through interaction with Miz-1. Proc. Natl. Acad. Sci.
USA 103, 4062-4067.
Ivics, Z, Izsvák, Z. (2006). Transposons for gene therapy! Curr.
Gene Ther. 6, 593-607.
Ivics, Z, Katzer, A, Stüwe, EE, Fiedler, D, Knespel, S, Izsvák, Z.
(2007). Targeted Sleeping Beauty transposition in human cells.
Mol. Ther. 15, 1137-1144.
Miskey, C, Papp, B, Mátés, L, Sinzelle, L, Keller, H, Izsvák, Z,
Ivics, Z. (2007). The ancient mariner sails again: Transposition
of the human Hsmar1 element by a reconstructed transposase
and activities of the SETMAR protein on transposon ends. Mol.
Cell. Biol. 27, 4589-600.
Cardiovascular and Metabolic Disease Research 59