Targeted disruption of FSCN2 gene induces retinopathy in mice.
OBJECTIVE
To investigate the morphology and function of photoreceptors in mice with mutation of the FSCN2 gene.


METHODS
A mouse line was generated carrying the 208delG mutation (point mutation, or p-type) and another with replacement of exon 1 by the cDNA of a green fluorescent protein (GFP knock-in, or g-type). The expression of retinal mRNA was determined by reverse transcription (RT)-polymerase chain reaction (PCR) and in situ hybridization performed on retinal sections. Morphologic analyses of the retinas were performed by light microscopy (LM) and transmission electron microscopy (TEM) and functional analyses by electroretinogram (ERG).


RESULTS
mRNA of FSCN2 was not detected in the retinal mRNA extracted from FSCN2p/p and FSCN2g/g mice. Both FSCN2(+/p) and FSCN2(+/g) mice had progressive photoreceptor degeneration with increasing age detected by LM and structural abnormalities of the outer segment (OS) detected by TEM. Both FSCN2(+/p) and FSCN2(+/g) mice had depressed rod and cone ERGs that worsened with increasing age.


CONCLUSIONS
These results indicate that haploinsufficiency of the FSCN2 gene may hamper maintenance and/or elongation of the OS disks and result in photoreceptor degeneration, as in human autosomal dominant retinitis pigmentosa.
Yokokura
Shunji
S
Department of Ophthalmology, Tohoku University School of Medicine, Miyagi, Japan. yokokura@oph.med.tohoku.ac.jp
Wada
Yuko
Y
Nakai
Shigeyasu
S
Sato
Hajime
H
Yao
Ryoji
R
Yamanaka
Hitomi
H
Ito
Sioko
S
Sagara
Yoshiko
Y
Takahashi
Mayumi
M
Nakamura
Yukie
Y
Tamai
Makoto
M
Noda
Tetsuo
T
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004596:Electroretinography; D005260:Female; D017353:Gene Deletion; D018390:Gene Targeting; D005799:Genes, Dominant; D049452:Green Fluorescent Proteins / Q000235:genetics; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics*; D020419:Photoreceptor Cells, Vertebrate / Q000648:ultrastructure*; D017354:Point Mutation; D012333:RNA, Messenger / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D008840:Microfilament Proteins; D012333:RNA, Messenger; C020324:fascin; D049452:Green Fluorescent Proteins