Abstract
Purpose: :
To define the genetic networks activated by optic nerve injury we examined gene expression in the retina of BXD recombinant inbred mouse strains (RI) 2 days after optic nerve crush.
Methods: :
The Illumina Sentrix BeadChip Array (MouseWG-6v2) was used to analyze mRNA levels in BXD RI strains along with the parental strains (C57Bl/6J and DBA/2J) and the reciprocal crosses for control retinas and retinas 2 days after optic nerve crush. The relative change in mRNA levels for each strain was used to construct the Retinal Injury Dataset (RID) that is presented in GeneNetwork (GN, genenetwork.org), along with a variety of powerful bioinformatics tools.
Results: :
In combination with GN, the RID provides a large resource for mapping, graphing, analyzing, and testing complex genetic networks. mRNA levels can be used to map quantitative trait loci (QTLs) that contribute to expression differences among the BXD strains and to establish links between classical phenotypes like ganglion cell loss and genomic sequence. We have used the RID to define genetic networks activated by optic nerve crush. Two networks are presented in this abstract. The first is the crystallin network. . Genes within this crystallin network include but are not limited to: Cryaa, Cryab, Cryba1, Cryba2, Cryba4, Crybb1, Crybb2, Crybb3, Crygb, Crygc, Crygn, Crygs, Grifin, Lim2, and Mip. Transcription of these genes is coregulated in the retina following optic nerve crush. One of the modulators found on chromosome 12 is lpin1. The second network is associated with the activation of Muller glial cells within the retina and includes many well known glial genes: Vim, Cd44 and Junb.
Conclusions: :
The variation in mRNA levels within BXD RI mouse strains and the changes occurring following optic nerve crush, make it possible to explore and to test expression networks underlying the response of the retina to injury. We present the first draft of the RID on GeneNetwork (genenetwork.org).
Keywords: gene microarray • optic nerve • crystallins