Brain phenotype of carbonic anhydrase IX-deficient mice

Pei-wen Pan (Corresponding Author), Anna-Kaisa Parkkila, Salla Autio, Mika Hilvo, Raija Sormunen, Silvia Pastorekova, Jaromir Pastorek, Hannu Haapasalo, Seppo Parkkila

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)163-176
JournalTransgenic Research
Volume21
Issue number1
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

carbonate dehydratase
Phenotype
brain
phenotype
mice
Brain
histology
Histology
genes
Genes
Molecular Sequence Annotation
Biological Phenomena
Mouse Car9 protein
Locomotion
Microarray Analysis
Oligonucleotide Array Sequence Analysis
transcriptomics
locomotion
homeostasis
Homeostasis

Keywords

  • Behavior
  • brain
  • carbonic anhydrase
  • cDNA microarray
  • knock-out mouse

Cite this

Pan, P., Parkkila, A-K., Autio, S., Hilvo, M., Sormunen, R., Pastorekova, S., ... Parkkila, S. (2012). Brain phenotype of carbonic anhydrase IX-deficient mice. Transgenic Research, 21(1), 163-176. https://doi.org/10.1007/s11248-011-9520-z
Pan, Pei-wen ; Parkkila, Anna-Kaisa ; Autio, Salla ; Hilvo, Mika ; Sormunen, Raija ; Pastorekova, Silvia ; Pastorek, Jaromir ; Haapasalo, Hannu ; Parkkila, Seppo. / Brain phenotype of carbonic anhydrase IX-deficient mice. In: Transgenic Research. 2012 ; Vol. 21, No. 1. pp. 163-176.
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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.",
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Pan, P, Parkkila, A-K, Autio, S, Hilvo, M, Sormunen, R, Pastorekova, S, Pastorek, J, Haapasalo, H & Parkkila, S 2012, 'Brain phenotype of carbonic anhydrase IX-deficient mice', Transgenic Research, vol. 21, no. 1, pp. 163-176. https://doi.org/10.1007/s11248-011-9520-z

Brain phenotype of carbonic anhydrase IX-deficient mice. / Pan, Pei-wen (Corresponding Author); Parkkila, Anna-Kaisa; Autio, Salla; Hilvo, Mika; Sormunen, Raija; Pastorekova, Silvia; Pastorek, Jaromir; Haapasalo, Hannu; Parkkila, Seppo.

In: Transgenic Research, Vol. 21, No. 1, 2012, p. 163-176.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Brain phenotype of carbonic anhydrase IX-deficient mice

AU - Pan, Pei-wen

AU - Parkkila, Anna-Kaisa

AU - Autio, Salla

AU - Hilvo, Mika

AU - Sormunen, Raija

AU - Pastorekova, Silvia

AU - Pastorek, Jaromir

AU - Haapasalo, Hannu

AU - Parkkila, Seppo

PY - 2012

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N2 - 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.

AB - 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.

KW - Behavior

KW - brain

KW - carbonic anhydrase

KW - cDNA microarray

KW - knock-out mouse

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DO - 10.1007/s11248-011-9520-z

M3 - Article

VL - 21

SP - 163

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JO - Transgenic Research

JF - Transgenic Research

SN - 0962-8819

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Pan P, Parkkila A-K, Autio S, Hilvo M, Sormunen R, Pastorekova S et al. Brain phenotype of carbonic anhydrase IX-deficient mice. Transgenic Research. 2012;21(1):163-176. https://doi.org/10.1007/s11248-011-9520-z