A naturally-occurring mutation in Cacna1f in a rat model of congenital stationary night blindness.
OBJECTIVE
To identify the gene mutation responsible for a previously described rat model of X-linked congenital stationary night blindness (CSNB).


METHODS
Rat orthologous genes for Nyx and Cacna1f were isolated from retina through rapid amplification the cDNA ends (RACE) and examined for mutations. Electroretinograms were used to identify affected animals.


RESULTS
The rat Nyx cDNA spans 1,971 nucleotides and encodes a protein of 476 amino acids (GenBank: DQ393414). The rat Cacna1f cDNA spans 6,076 nucleotides and encodes a protein of 1,980 amino acids (GenBank: DQ393415). A c.2941C>T (p.R981Stop) mutation in Cacna1f was found in affected rats. Immunochemistry study showed labeling for rod bipolar and horizontal cells were reduced in affect retinas. For affected rats, b-wave and oscillatory potentials of scotopic ERG were absent, and b-wave of photopic ERG was clear but obviously reduced.


CONCLUSIONS
The Cacna1f mutation identified in the rat model of CSNB was predicted to lead to a protein product that is shortened by 999 amino acids, indicating that this is a model for the incomplete subtype of human X-linked CSNB (CSNB2). This rat model will be useful for defining the pathophysiological properties of this human disorder.
Gu
Yonghao
Y
Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
Wang
Lifeng
L
Zhou
Jie
J
Guo
Qun
Q
Liu
Na
N
Ding
Zhenqiang
Z
Li
Li
L
Liu
Xinping
X
An
Jing
J
Yan
Guolin
G
Yao
Libo
L
Zhang
Zuoming
Z
D000221:Adaptation, Ocular; D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D003596:Cytosine; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000302:isolation & purification; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D009154:Mutation; D009755:Night Blindness / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics; D051381:Rats / Q000235:genetics*; D012160:Retina / Q000473:pathology; D051245:Retinal Bipolar Cells / Q000473:pathology; D051248:Retinal Horizontal Cells / Q000473:pathology; D013941:Thymine
C527361:Cacna1f protein, rat; D015220:Calcium Channels; D018076:DNA, Complementary; C527362:Nyx protein, rat; D011509:Proteoglycans; D003596:Cytosine; D013941:Thymine