Genetic networks in the mouse retina

Growth associated protein 43 and phosphatase tensin homolog network

Natalie E. Freeman, Justin P. Templeton, William E. Orr, Lu Lu, Robert Williams, Eldon E. Geisert

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Purpose: The present study examines the structure and covariance of endogenous variation in gene expression across the recently expanded family of C57BL/6J (B) X DBA/2J (D) Recombinant Inbred (BXD RI) strains of mice. This work is accompanied by a highly interactive database that can be used to generate and test specific hypotheses. For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten). Methods: The Hamilton Eye Institute (HEI) Retina Database within GeneNetwork features the data analysis of 346 Illumina Sentrix BeadChip Arrays (mouse whole genome-6 version 2). Eighty strains of mice are presented, including 75 BXD RI strains, the parental strains (C57BL/6J and DBA/2J), the reciprocal crosses, and the BALB/cByJ mice. Independent biologic samples for at least two animals from each gender were obtained with a narrow age range (48 to 118 days). Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. The data was globally normalized with rank invariant and stabilization (2z+8). Results: The HEI Retina Database is located on the GeneNetwork website. The database was used to extract unique transcriptome signatures for specific cell types in the retina (retinal pigment epithelial, amacrine, and retinal ganglion cells). Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database. Bioinformatic tools located within GeneNetwork in conjunction with the HEI Retina Database were used to identify the unique signature Quantitative Trait Loci (QTLs) for Gap43 and Pten on chromosomes 1, 2, 12, 15, 16, and 19. Gap43 and Pten possess networks that are similar to ganglion cell networks that may be associated with axonal growth in the mouse retina. This network involves high correlations of transcription factors (SRY sex determining region Y-box 2 [Sox2], paired box gene 6 [Pax6], and neurogenic differentiation 1 [Neurod1]), and genes involved in DNA binding (proliferating cell nuclear antigen [Pcna] and zinc finger, BED-type containing 4 [Zbed4]), as well as an inhibitor of DNA binding (inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [Id2]). Furthermore, we identified the potential upstream modifiers on chromosome 2 (teashirt zinc finger homeobox 2 [Tshz2], RNA export 1 homolog [Rae1] and basic helix-loop-helix domain contatining, class B4 [Bhlhb4]) on chromosome 15 (RAB, member of RAS oncogene family-like 2a [Rabl2a], phosphomannomutase 1 [Pmm1], copine VIII [Cpne8], and fibulin 1 [Fbln1]). Conclusions: The endogenous variation in mRNA levels among BXD RI strains can be used to explore and test expression networks underlying variation in retina structure, function, and disease susceptibility. The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

Original languageEnglish (US)
Pages (from-to)1355-1372
Number of pages18
JournalMolecular vision
Volume17
StatePublished - Jun 22 2011

Fingerprint

GAP-43 Protein
Phosphoprotein Phosphatases
Retina
Databases
Chromosomes, Human, Pair 2
Zinc Fingers
DNA
Helix-Loop-Helix Motifs
RNA
Genes
Gene Expression
Chromosomes, Human, Pair 15
Complementary RNA
Retinal Pigments
Tensins
Retinal Ganglion Cells
Homeobox Genes
Chromosomes, Human, Pair 1
Quantitative Trait Loci
Disease Susceptibility

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Genetic networks in the mouse retina : Growth associated protein 43 and phosphatase tensin homolog network. / Freeman, Natalie E.; Templeton, Justin P.; Orr, William E.; Lu, Lu; Williams, Robert; Geisert, Eldon E.

In: Molecular vision, Vol. 17, 22.06.2011, p. 1355-1372.

Research output: Contribution to journalArticle

Freeman, Natalie E. ; Templeton, Justin P. ; Orr, William E. ; Lu, Lu ; Williams, Robert ; Geisert, Eldon E. / Genetic networks in the mouse retina : Growth associated protein 43 and phosphatase tensin homolog network. In: Molecular vision. 2011 ; Vol. 17. pp. 1355-1372.
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abstract = "Purpose: The present study examines the structure and covariance of endogenous variation in gene expression across the recently expanded family of C57BL/6J (B) X DBA/2J (D) Recombinant Inbred (BXD RI) strains of mice. This work is accompanied by a highly interactive database that can be used to generate and test specific hypotheses. For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten). Methods: The Hamilton Eye Institute (HEI) Retina Database within GeneNetwork features the data analysis of 346 Illumina Sentrix BeadChip Arrays (mouse whole genome-6 version 2). Eighty strains of mice are presented, including 75 BXD RI strains, the parental strains (C57BL/6J and DBA/2J), the reciprocal crosses, and the BALB/cByJ mice. Independent biologic samples for at least two animals from each gender were obtained with a narrow age range (48 to 118 days). Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. The data was globally normalized with rank invariant and stabilization (2z+8). Results: The HEI Retina Database is located on the GeneNetwork website. The database was used to extract unique transcriptome signatures for specific cell types in the retina (retinal pigment epithelial, amacrine, and retinal ganglion cells). Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database. Bioinformatic tools located within GeneNetwork in conjunction with the HEI Retina Database were used to identify the unique signature Quantitative Trait Loci (QTLs) for Gap43 and Pten on chromosomes 1, 2, 12, 15, 16, and 19. Gap43 and Pten possess networks that are similar to ganglion cell networks that may be associated with axonal growth in the mouse retina. This network involves high correlations of transcription factors (SRY sex determining region Y-box 2 [Sox2], paired box gene 6 [Pax6], and neurogenic differentiation 1 [Neurod1]), and genes involved in DNA binding (proliferating cell nuclear antigen [Pcna] and zinc finger, BED-type containing 4 [Zbed4]), as well as an inhibitor of DNA binding (inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [Id2]). Furthermore, we identified the potential upstream modifiers on chromosome 2 (teashirt zinc finger homeobox 2 [Tshz2], RNA export 1 homolog [Rae1] and basic helix-loop-helix domain contatining, class B4 [Bhlhb4]) on chromosome 15 (RAB, member of RAS oncogene family-like 2a [Rabl2a], phosphomannomutase 1 [Pmm1], copine VIII [Cpne8], and fibulin 1 [Fbln1]). Conclusions: The endogenous variation in mRNA levels among BXD RI strains can be used to explore and test expression networks underlying variation in retina structure, function, and disease susceptibility. The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.",
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T1 - Genetic networks in the mouse retina

T2 - Growth associated protein 43 and phosphatase tensin homolog network

AU - Freeman, Natalie E.

AU - Templeton, Justin P.

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AU - Lu, Lu

AU - Williams, Robert

AU - Geisert, Eldon E.

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N2 - Purpose: The present study examines the structure and covariance of endogenous variation in gene expression across the recently expanded family of C57BL/6J (B) X DBA/2J (D) Recombinant Inbred (BXD RI) strains of mice. This work is accompanied by a highly interactive database that can be used to generate and test specific hypotheses. For example, we define the genetic network regulating growth associated protein 43 (Gap43) and phosphatase tensin homolog (Pten). Methods: The Hamilton Eye Institute (HEI) Retina Database within GeneNetwork features the data analysis of 346 Illumina Sentrix BeadChip Arrays (mouse whole genome-6 version 2). Eighty strains of mice are presented, including 75 BXD RI strains, the parental strains (C57BL/6J and DBA/2J), the reciprocal crosses, and the BALB/cByJ mice. Independent biologic samples for at least two animals from each gender were obtained with a narrow age range (48 to 118 days). Total RNA was prepared followed by the production of biotinylated cRNAs, which were pipetted into the Mouse WG-6V2 arrays. The data was globally normalized with rank invariant and stabilization (2z+8). Results: The HEI Retina Database is located on the GeneNetwork website. The database was used to extract unique transcriptome signatures for specific cell types in the retina (retinal pigment epithelial, amacrine, and retinal ganglion cells). Two genes associated with axonal outgrowth (Gap43 and Pten) were used to display the power of this new retina database. Bioinformatic tools located within GeneNetwork in conjunction with the HEI Retina Database were used to identify the unique signature Quantitative Trait Loci (QTLs) for Gap43 and Pten on chromosomes 1, 2, 12, 15, 16, and 19. Gap43 and Pten possess networks that are similar to ganglion cell networks that may be associated with axonal growth in the mouse retina. This network involves high correlations of transcription factors (SRY sex determining region Y-box 2 [Sox2], paired box gene 6 [Pax6], and neurogenic differentiation 1 [Neurod1]), and genes involved in DNA binding (proliferating cell nuclear antigen [Pcna] and zinc finger, BED-type containing 4 [Zbed4]), as well as an inhibitor of DNA binding (inhibitor of DNA binding 2, dominant negative helix-loop-helix protein [Id2]). Furthermore, we identified the potential upstream modifiers on chromosome 2 (teashirt zinc finger homeobox 2 [Tshz2], RNA export 1 homolog [Rae1] and basic helix-loop-helix domain contatining, class B4 [Bhlhb4]) on chromosome 15 (RAB, member of RAS oncogene family-like 2a [Rabl2a], phosphomannomutase 1 [Pmm1], copine VIII [Cpne8], and fibulin 1 [Fbln1]). Conclusions: The endogenous variation in mRNA levels among BXD RI strains can be used to explore and test expression networks underlying variation in retina structure, function, and disease susceptibility. The Gap43 and Pten network highlights the covariance of gene expression and forms a molecular network associated with axonal outgrowth in the adult retina.

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