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01-12-2022 | Hydrocephalus | Research

Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study

Authors: Hanbing Xu, Masakazu Miyajima, Madoka Nakajima, Ikuko Ogino, Kaito Kawamura, Chihiro Akiba, Chihiro Kamohara, Koichiro Sakamoto, Kostadin Karagiozov, Eri Nakamura, Nobuhiro Tada, Hajime Arai, Akihide Kondo

Published in: Fluids and Barriers of the CNS | Issue 1/2022

Abstract

Background

Congenital hydrocephalus occurs with some inheritable characteristics, but the mechanisms of its development remain poorly understood. Animal models provide the opportunity to identify potential genetic causes in this condition. The Hydrocephalus-Texas (H-Tx) rat strain is one of the most studied animal models for investigating the causative genetic alterations and analyzing downstream pathogenetic mechanisms of congenital hydrocephalus.

Methods

Comparative genomic hybridization (CGH) array on non-hydrocephalic and hydrocephalic H-Tx rats was used to identify causative genes of hydrocephalus. Targeted gene knockout mice were generated by CRISPR/Cas9 to study the role of this gene in hydrocephalus.

Results

CGH array revealed a copy number loss in chromosome 16p16 region in hydrocephalic H-Tx rats at 18 days gestation, encompassing the protein tyrosine phosphatase non-receptor type 20 (Ptpn20), a non-receptor tyrosine phosphatase, without change in most non-hydrocephalic H-Tx rats. Ptpn20-knockout (Ptpn20^−/−) mice were generated and found to develop ventriculomegaly at 8 weeks. Furthermore, high expression of phosphorylated Na-K-Cl cotransporter 1 (pNKCC1) was identified in the choroid plexus (CP) epithelium of mice lacking Ptpn20 from 8 weeks until 72 weeks.

Conclusions

This study determined the chromosomal location of the hydrocephalus-associated Ptpn20 gene in hydrocephalic H-Tx rats. The high level of pNKCC1 mediated by Ptpn20 deletion in CP epithelium may cause overproduction of cerebrospinal fluid and contribute to the formation of hydrocephalus in Ptpn20^−/− mice. Ptpn20 may be a potential therapeutic target in the treatment of hydrocephalus.

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Title: Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study
Authors: Hanbing Xu
Masakazu Miyajima
Madoka Nakajima
Ikuko Ogino
Kaito Kawamura
Chihiro Akiba
Chihiro Kamohara
Koichiro Sakamoto
Kostadin Karagiozov
Eri Nakamura
Nobuhiro Tada
Hajime Arai
Akihide Kondo
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Hydrocephalus
Hydrocephalus
Hydrocephalus
Published in: Fluids and Barriers of the CNS / Issue 1/2022
Electronic ISSN: 2045-8118
DOI: https://doi.org/10.1186/s12987-022-00341-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Ptpn20 deletion in H-Tx rats enhances phosphorylation of the NKCC1 cotransporter in the choroid plexus: an evidence of genetic risk for hydrocephalus in an experimental study

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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