Multiple genes on chromosome 7 regulate dopaminergic amacrine cell number in the mouse retina

Irene E. Whitney, Mary A. Raven, Daniel C. Ciobanu, Robert W. Williams, Benjamin E. Reese

Research output: Contribution to journalArticle

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Abstract

PURPOSE: The size of neuronal populations is modulated bygene variants that influence cell production and survival, in turn influencing neuronal connectivity, function, and disease risk. The size of the dopaminergic amacrine (DA) cell popula-tion is a highly heritable trait exhibiting sixfold variation among inbred strains of mice and is used here to identify genes that modulate the number of DA cells. METHODS: The entire population was counted in retinal whole- mounts from 37 genetically defined lines of mice, including six standard inbred strains, 25 recombinant inbred strains (AXB/ BXA), reciprocal F1 hybrids, a chromosome (Chr) 7 consomic line, and three additional genetically modified lines. RESULTS: Much of this variation was mapped to a broad locus on Chr 7 (Dopaminergic amacrine cell number control, Chr 7 [Dacnc7]). The Dacnc7 locus is flanked by two candidate genes known to modulate the number of other types of retinal neuron-the proapoptotic gene, Bax, and tyrosinase. The Tyr mutation was shown to modulate DA cell number modestly, though in the direction opposite that predicted. In contrast, Bax deficiency increased the population fourfold. Bax expres- sion was significantly greater in the A/J than in the C57BL/6J strain, an effect that may be attributed to an SNP in a p53 consensus binding site known to modulate transcription. Fi- nally, we note a strong candidate situated at the peak of the Dacnc7 locus, Lrrk1, a Parkinson's disease gene exhibiting missense mutations segregating within the AXB/BXA cross. CONCLUSIONS. Multiple polymorphic genes on Chr 7 modulate the size of the population of DA cells.

Original languageEnglish (US)
Pages (from-to)1996-2003
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume50
Issue number5
DOIs
StatePublished - Dec 1 2009

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Amacrine Cells
Chromosomes, Human, Pair 7
Retina
Cell Count
Genes
Population Density
Retinal Neurons
Inbred Strains Mice
Monophenol Monooxygenase
Missense Mutation
Population
Single Nucleotide Polymorphism
Parkinson Disease
Cell Survival
Binding Sites
Mutation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Multiple genes on chromosome 7 regulate dopaminergic amacrine cell number in the mouse retina. / Whitney, Irene E.; Raven, Mary A.; Ciobanu, Daniel C.; Williams, Robert W.; Reese, Benjamin E.

In: Investigative Ophthalmology and Visual Science, Vol. 50, No. 5, 01.12.2009, p. 1996-2003.

Research output: Contribution to journalArticle

Whitney, Irene E. ; Raven, Mary A. ; Ciobanu, Daniel C. ; Williams, Robert W. ; Reese, Benjamin E. / Multiple genes on chromosome 7 regulate dopaminergic amacrine cell number in the mouse retina. In: Investigative Ophthalmology and Visual Science. 2009 ; Vol. 50, No. 5. pp. 1996-2003.
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