title: Brain phenotype of carbonic anhydrase IX-deficient mice.
abstract: Preliminary observations have suggested mild behavioral changes and a morphological disruption of brain histology in 1.5-year-old carbonic anhydrase IX (CA IX)-deficient (Car9 (-/-)) mice. These findings led us to design a 1-year follow-up study in which the behavior and brain histology of Car9 (-/-) and wild-type mice were monitored. Morphological analysis revealed vacuolar degenerative changes in the brains of Car9 (-/-) mice. The changes became visible at the age of eight to ten months. Behavioral tests showed that the Car9 (-/-) mice exhibited abnormal locomotor activity and poor performance in a memory test. To further identify the transcriptomic responses to CA IX deficiency in the brain, genome-wide cDNA microarray analyses were performed. Thirty-one and 37 genes were significantly up- or down-regulated, respectively, in the brain of Car9 (-/-) mice compared to the wild-type mice. Functional annotation revealed that the genes with increased expression were involved in several processes, such as RNA metabolism, and the genes with reduced expression were implicated in other important processes, including the regulation of cellular ion homeostasis. Notably, the biological processes "behavior" and "locomotory behavior" were the two prominent terms overrepresented among the down-regulated genes, which is consistent with the behavioral phenotype. These results suggest that CA IX may directly or indirectly play novel functions in brain tissue. Furthermore, the brain phenotype of Car9 (-/-) mice seems to be age-dependent. The results indicate that the functional changes precede the microscopic alterations in the brains of Car9 (-/-) mice.
authors.affiliation: Institute of Medical Technology, University of Tampere, Biokatu 6, 33520, Tampere, Finland. peiwen.pan@uta.fi
authors.forename: Pei-wen
authors.initials: PW
authors.lastname: Pan
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Parkkila
authors.forename: Salla
authors.initials: S
authors.lastname: Autio
authors.forename: Mika
authors.initials: M
authors.lastname: Hilvo
authors.forename: Raija
authors.initials: R
authors.lastname: Sormunen
authors.forename: Silvia
authors.initials: S
authors.lastname: Pastorekova
authors.forename: Jaromir
authors.initials: J
authors.lastname: Pastorek
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology* / Q000502:physiology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics*; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype
chemical_list: D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C492796:Car9 protein, mouse