Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish
Aspatwar, Ashok ; Tolvanen, Martti E. E. ; Jokitalo, Eija ; Parikka, Mataleena ; Ortutay, Csaba ; Harjula, Sanna-Kaisa E. ; Ramet, Mika ; Vihinen, Mauno LU
and Parkkila, Seppo
(2013)
In Human Molecular Genetics
22(3).
p.417-432
- Abstract
- Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema... (More)
- Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3470455
- author
- Aspatwar, Ashok
; Tolvanen, Martti E. E.
; Jokitalo, Eija
; Parikka, Mataleena
; Ortutay, Csaba
; Harjula, Sanna-Kaisa E.
; Ramet, Mika
; Vihinen, Mauno
LU
and Parkkila, Seppo
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Human Molecular Genetics
- volume
- 22
- issue
- 3
- pages
- 417 - 432
- publisher
- Oxford University Press
- external identifiers
-
- wos:000313531500001
- scopus:84872425070
- pmid:23087022
- ISSN
- 0964-6906
- DOI
- 10.1093/hmg/dds438
- language
- English
- LU publication?
- yes
- id
- d9869559-bf96-4728-a9f9-d9710119d737 (old id 3470455)
- date added to LUP
- 2016-04-01 10:26:21
- date last changed
- 2022-04-27 22:03:01
@article{d9869559-bf96-4728-a9f9-d9710119d737,
abstract = {{Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans.}},
author = {{Aspatwar, Ashok and Tolvanen, Martti E. E. and Jokitalo, Eija and Parikka, Mataleena and Ortutay, Csaba and Harjula, Sanna-Kaisa E. and Ramet, Mika and Vihinen, Mauno and Parkkila, Seppo}},
issn = {{0964-6906}},
language = {{eng}},
number = {{3}},
pages = {{417--432}},
publisher = {{Oxford University Press}},
series = {{Human Molecular Genetics}},
title = {{Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish}},
url = {{http://dx.doi.org/10.1093/hmg/dds438}},
doi = {{10.1093/hmg/dds438}},
volume = {{22}},
year = {{2013}},
}