Genetic modulation of horizontal cell number in the mouse retina

Irene E. Whitney, Mary A. Raven, Daniel C Ciobanu, Ross A. Poché, Qian Ding, Yasser Elshatory, Lin Gan, Robert W. Williams, Benjamin E. Reese

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Neuronal populations display conspicuous variability in their size among individuals, but the genetic sources of this variation are largely undefined. We demonstrate a large and highly heritable variation in neuron number within the mouse retina, affecting a critical population of interneurons, the horizontal cells. Variation in the size of this population maps to the distal end of chromosome (Chr) 13, a region homologous to human Chr 5q11.1-11.2. This region contains two genes known to modulate retinal cell number. Using conditional knock-out mice, we demonstrate that one of these genes, the LIM homeodomain gene Islet-1 (Isl1), plays a role in regulating horizontal cell number. Genetic differences in Isl1 expression are high during the period of horizontal cell production, and cis-regulation of Isl1 expression within the retina is demonstrated directly. We identify a single nucleotide polymorphism in the 5′ UTR of Isl1 that creates an E-box sequence as a candidate causal variant contributing to this variation in horizontal cell number.

Original languageEnglish (US)
Pages (from-to)9697-9702
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number23
DOIs
StatePublished - Jun 7 2011

Fingerprint

Retina
Cell Count
E-Box Elements
Genes
Chromosomes, Human, Pair 13
5' Untranslated Regions
Human Chromosomes
Interneurons
Population Density
Knockout Mice
Population
Single Nucleotide Polymorphism
Neurons

Keywords

  • Allele-specific expression
  • Follistatin
  • Quantitative trait locus
  • Recombinant inbred strain

ASJC Scopus subject areas

  • General

Cite this

Genetic modulation of horizontal cell number in the mouse retina. / Whitney, Irene E.; Raven, Mary A.; Ciobanu, Daniel C; Poché, Ross A.; Ding, Qian; Elshatory, Yasser; Gan, Lin; Williams, Robert W.; Reese, Benjamin E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 23, 07.06.2011, p. 9697-9702.

Research output: Contribution to journalArticle

Whitney, IE, Raven, MA, Ciobanu, DC, Poché, RA, Ding, Q, Elshatory, Y, Gan, L, Williams, RW & Reese, BE 2011, 'Genetic modulation of horizontal cell number in the mouse retina', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 23, pp. 9697-9702. https://doi.org/10.1073/pnas.1103253108
Whitney, Irene E. ; Raven, Mary A. ; Ciobanu, Daniel C ; Poché, Ross A. ; Ding, Qian ; Elshatory, Yasser ; Gan, Lin ; Williams, Robert W. ; Reese, Benjamin E. / Genetic modulation of horizontal cell number in the mouse retina. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 23. pp. 9697-9702.
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