Conditional Mice Mutants as Tools for Studying Genetic Disorders and Eye Physiology

Conditional Mice Mutants as Tools for Studying Genetic Disorders and Eye Physiology

RNDr. Zbynek Kozmik , CSc.

RNDr. Zbynek Kozmik , CSc. — Project head

About us

The mouse model represents an attractive alternative for studying the development and pathogenesis of the human eye. Currently, a systematic targeted mutagenesis of mice genes in the embryonic stem cells is being done (EUCOMM and KOMP consortia). Shortly, the conditional mutants for the majority of the genes will be available for phenotypic analysis. Their utility is, to a great extent, dependent on the availability of suitable strains of mice with the tissue or time limited activity of the Cre recombinase.

For each area of interest, e.g. eye, brain, liver, it is necessary to have a panel of the Cre-transgenic mouse strains which enable a specific deletion of the given gene and a detailed study of its function in the context of the whole organism. The size of the Cre panel which it is necessary to create, is dependent primarily on the complexity of an organ (number of cellular types, development stages), but also by the current availability of Cre lines for the given organ.

For instance, the Cre expression in the very early embryonic retina, in certain types of retinal cells of an adult mouse and in the lens and the cornea of an adult mouse is not available for the functional genomics of the eye so far.

The project will be focused on the systematic preparation of new transgenic Cre lines with defined expressions in the eye tissues and the consecutive usage of the Cre lines for the systematic analysis of the conditional mutants in genes coding the transcriptional factors and components of the Wnt signaling pathway.

The new transgenic mice lines with the tissue and time limited activity of the Cre recombinase will be prepared in the presented project. Their utility will be verified by the deletion of genes which have the known pathogenesis. Then the suitable Cre lines will be used for the systematic gene deletions and the study of their function in eye tissues. The project will contribute to our understanding of eye diseases.

Goal:

  • To prepare the transgenic Cre constructs with the BAC recombineering technology and with their help to create the Cre lines for the functional genomic of the early retina and adult cornea,
  • to prepare the transgenic constructs with the pharmacologically controlled form of the Cre recombinase (Cre-ERTM) and to create the Cre lines with time conditioned activity of the Cre recombinase,
  • to map the function of the genes encoding transcription factors and components of the Wnt signaling pathway in the eye tissues.

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Publications

2018

Fujimura N, Kuzelova A, Ebert A, Strnad H, Lachova J, Machon O, Busslinger M, Kozmik Z: Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation. Dev Biol 2018 433(1): 47-60.

2017

Pantzartzi CN, Pergner J, Kozmikova I, Kozmik Z: The opsin repertoire of the European lancelet: a window into light detection in a basal chordate. Int J Dev Biol 2017 61(10-11-12): 763-772.

2016

Antosova B, Smolikova J, Klimova L, Lachova J, Bendova M, Kozmikova I, Machon O, Kozmik Z: The Gene Regulatory Network of Lens Induction Is Wired through Meis-Dependent Shadow Enhancers of Pax6. PLoS Genet 2016 12(12): e1006441.

Fujimura N: WNT/β-Catenin Signaling in Vertebrate Eye Development. Front Cell Dev Biol 2016 4: 138

Team

RNDr. Zbynek Kozmik , CSc.

RNDr.
Zbynek Kozmik , CSc.

Head of Group Conditional Mice Mutants as Tools for Studying Genetic Disorders and Eye Physiology

zbynek.kozmik@img.cas.cz
+420325873101

Ing.
Jitka Láchová

jitka.lachova@img.cas.cz

Naoko Dupačová , Ph.D.

fujimura@img.cas.cz

Mgr.
Jana Smolíková, Ph.D.

jana.smolikova@img.cas.cz

Ing.
Anna Zitová

anna.stvanova@img.cas.cz