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The use of yeast artificial chromosomes in transgenic animals: expression studies of the tyrosinase gene in

P Giraldo¹, E Giménez, L Montoliu

¹Departamento de Biología Molecular y Celular, Centro Nacional de Biotecnología, Madrid, Spain.

Genetic Analysis : Biomolecular Engineering

|December 22, 1999

Summary

Researchers observed variegation and inherited somatic mosaicism in transgenic mice with deleted DNAse I hypersensitive sites (HS) near the tyrosinase gene. New transgenic models with smaller HS deletions are currently being generated to further investigate these findings.

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Area of Science:

Genetics
Molecular Biology
Developmental Biology

Background:

Variegation and inherited somatic mosaicism are phenomena observed in genetic studies.
Transgenic mouse models are crucial for investigating gene function and regulation.
Yeast artificial chromosomes (YACs) allow for the study of large genomic regions.

Purpose of the Study:

To investigate the role of a specific DNAse I hypersensitive site (HS) in gene regulation.
To understand the mechanisms behind variegation and inherited somatic mosaicism in transgenic organisms.
To generate and analyze new transgenic mouse models with targeted deletions of the HS.

Main Methods:

Generation of transgenic mice carrying yeast artificial chromosomes (YACs).
Targeted deletion of a DNAse I hypersensitive site (HS) located upstream of the mouse tyrosinase gene.
Observation and analysis of variegation and inherited somatic mosaicism phenotypes.

Main Results:

Deletion of the HS resulted in observed variegation and inherited somatic mosaicism in transgenic mice.
The specific HS plays a role in the stable expression or regulation of the mouse tyrosinase gene.
These findings suggest a link between the deleted HS and developmental genetic instability.

Conclusions:

The DNAse I hypersensitive site (HS) is critical for preventing variegation and inherited somatic mosaicism.
Further studies with minor deletions of the HS are needed to precisely map regulatory elements.
Transgenic mouse models provide valuable insights into gene regulation and mosaicism.