Hydrocephalus in a rat model of Meckel Gruber syndrome with a TMEM67 mutation.
Animals
Brain
/ metabolism
Chlorides
/ cerebrospinal fluid
Choroid Plexus
/ metabolism
Ciliary Motility Disorders
/ genetics
Encephalocele
/ genetics
Female
Hydrocephalus
/ genetics
Membrane Proteins
/ genetics
Mutation
/ genetics
Polycystic Kidney Diseases
/ genetics
Potassium
/ cerebrospinal fluid
Rats
Retinitis Pigmentosa
/ genetics
Sodium
/ cerebrospinal fluid
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
31 01 2019
31 01 2019
Historique:
received:
11
04
2018
accepted:
05
12
2018
entrez:
2
2
2019
pubmed:
2
2
2019
medline:
15
9
2020
Statut:
epublish
Résumé
Transmembrane protein 67 (TMEM67) is mutated in Meckel Gruber Syndrome type 3 (MKS3) resulting in a pleiotropic phenotype with hydrocephalus and renal cystic disease in both humans and rodent models. The precise pathogenic mechanisms remain undetermined. Herein it is reported for the first time that a point mutation of TMEM67 leads to a gene dose-dependent hydrocephalic phenotype in the Wistar polycystic kidney (Wpk) rat. Animals with TMEM67 heterozygous mutations manifest slowly progressing hydrocephalus, observed during the postnatal period and continuing into adulthood. These animals have no overt renal phenotype. The TMEM67 homozygous mutant rats have severe ventriculomegaly as well as severe polycystic kidney disease and die during the neonatal period. Protein localization in choroid plexus epithelial cells indicates that aquaporin 1 and claudin-1 both remain normally polarized in all genotypes. The choroid plexus epithelial cells may have selectively enhanced permeability as evidenced by increased Na
Identifiants
pubmed: 30705305
doi: 10.1038/s41598-018-37620-5
pii: 10.1038/s41598-018-37620-5
pmc: PMC6355840
doi:
Substances chimiques
Chlorides
0
Membrane Proteins
0
Sodium
9NEZ333N27
Potassium
RWP5GA015D
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1069Subventions
Organisme : NHLBI NIH HHS
ID : T32 HL007224
Pays : United States
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