Generation of knock-in mice carrying third cones with spectral sensitivity different from S and L cones.
Red-green color vision in primates is unique in the sense that it is mediated by two photoreceptor cells that are indistinguishable in all aspects except for their visual pigments. In order to generate an animal model for investigation of the interaction between red-green inputs at the molecular level, we applied knock-in technology and X-chromosome inactivation machinery to make a mouse model with cone cells possessing visual pigments with different spectral sensitivities. We introduced a S308A point mutation into the Green opsin gene allele on the X-chromosome. This manipulation generated a 24 nm red-shift of absorption maximum in the cone pigment with negligible functional differences in other molecular properties. Amplitudes of responses in ERG and ganglion cell recordings of homozygotes were similar to those of wild-types, although the spectral sensitivities differed. Heterozygotes showed variable spectral sensitivities of ganglion cell responses due to the different integration of the native and the S308A cone inputs on the dendritic fields. In situ hybridization experiments showed that cone cells with respective pigments formed patch-like clusters of specific L cone-types, approximately 30 mum in diameter, which were randomly distributed in the dorsal region of the retinas. Since the patch-like clustering was arranged by X-inactivation, such clustering could be present in the peripheral retinas of New World monkeys with polymorphic L pigments, indicating that our mice would be a suitable model to study evolution of the mammalian color vision system.
Onishi
Akishi
A
Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
Hasegawa
Jun
J
Imai
Hiroo
H
Chisaka
Osamu
O
Ueda
Yoshiki
Y
Honda
Yoshihito
Y
Tachibana
Masao
M
Shichida
Yoshinori
Y
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003118:Color Perception / Q000502:physiology; D004596:Electroretinography; D005091:Exons / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice / Q000235:genetics*; D023421:Models, Animal; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017949:Retinal Cone Photoreceptor Cells / Q000033:anatomy & histology / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D012168:Retinal Pigments / Q000235:genetics*; D017299:Rod Opsins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013056:Spectrophotometry, Ultraviolet; D049951:X Chromosome Inactivation / Q000235:genetics*
D012168:Retinal Pigments; D017299:Rod Opsins; C095854:middle-wavelength opsin; D019204:GTP-Binding Proteins