title: Genetic pathways regulating glutamate levels in retinal Müller cells.
abstract: Müller cells serve many functions including the regulation of extracellular glutamate levels. The product of two genes, Slc1a3 [aka solute carrier family 1 (glial high affinity glutamate transporter), member 3] and Glul (aka glutamine synthetase) are the primary role players that transport glutamate into the Müller cell and convert it into glutamine. In this study, we sought to identify the genetic regulation of both genes. Given their tightly coupled biological functions, we predicted that they would be similarly regulated. Using an array of 75 recombinant inbred strains of mice, we determined that Slc1a3 and Glul are differentially regulated by distinct chromosomal regions. Interestingly, despite their independent regulation, gene ontology analysis of tightly correlated genes reveals that the enriched and statistically significant molecular function categories of both directed acyclic graphs have substantial overlap, indicating that the shared functions of correlates of Slc1a3 and Glul include production and usage of ATP.
authors.affiliation: Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA. mjablonski@uthsc.edu
authors.forename: Monica M
authors.initials: MM
authors.lastname: Jablonski
authors.forename: Natalie E
authors.initials: NE
authors.lastname: Freeman
authors.forename: William E
authors.initials: WE
authors.lastname: Orr
authors.forename: Justin P
authors.initials: JP
authors.lastname: Templeton
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Robert W
authors.initials: RW
authors.lastname: Williams
authors.forename: Eldon E
authors.initials: EE
authors.lastname: Geisert
mesh_terms: D000818:Animals; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics*; D018698:Glutamic Acid / Q000378:metabolism*; D051379:Mice; D009693:Nucleic Acid Hybridization; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012160:Retina / Q000166:cytology / Q000378:metabolism*
chemical_list: D027341:Excitatory Amino Acid Transporter 1; C493393:Slc1a3 protein, mouse; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase