In one mouse's left and right retinas, cells that silenced the maternal X chromosome are red and those that silenced the paternal X chromosome are green.NATHANS LAB, COURTESY OF NEURONIn every female eutherian mammalian cell, one of the two X chromosomes is inactivated. Though visual representations of X inactivation are well known—the pattern of a calico cat’s fur, for instance—understanding of how X chromosome inactivation affects disease and development is still limited. Now, Jeremy Nathans of Johns Hopkins University School of Medicine and his colleagues have generated transgenic mice in which X chromosome inactivation can be visualized in individual cells. The work was published this month (January 8) in Neuron.
The researchers generated mouse lines with Cre-inducible, nuclear-localized fluorescent reporters—either green fluorescent protein (GFP) or tdTomato, a red fluorescent protein—inserted into the locus for the X-linked Hprt gene. Each mouse line used a tissue-specific promoter to drive Cre, and the red and green fluorescent lines were bred to generate heterozygous females containing one of each X chromosome. The team analyzed the green and red fluorescence in each cell in which Cre was expressed, and found that the patterns of X inactivation varied widely from tissue to tissue and sometimes showed distinct left-right asymmetry. Variable X inactivation led to differences in the manifestation of an X-linked disease that affects blood vessels in the retina and contributed to biological diversity in the central nervous system.
“Diversity in ...