- Email: [email protected]
A thyroid hormone receptor that is required for the development of green cone photoreceptors
transgene DNA and messenger RNA. All tissues that were studied from a fraternal set of twins, miscarried at 73 days, carried the transgene, as confirmed by Southern blot analysis, and the GFP transgene reporter was detected by both direct and indirect fluorescence imaging. Molecular approaches for making clones, utilizing stem cells and producing transgenic monkeys, could be combined to produce models that bridge the gap between transgenic mice and humans.—Hans E. Grossniklaus *Departments of Cell-Developmental Biology and Obstetrics-Gynecology, Oregon Health Sciences University, 505 NW 185th Avenue, Beaverton, OR 97006. E-mail: [email protected].
● A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, Petrukhin K.* Nat Genet 2001;27:89 –93.
S
TARGARDT-LIKE MACULAR DYSTROPHY (STGD3, MIM
600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. The authors limited the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long
VOL. 131, NO. 5
chain fatty acids. The authors feel that they are the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration. *Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania. E-mail: [email protected].
●
A thyroid hormone receptor that is required for the development of green cone photoreceptors. Ng L, Hurley JB, Dierks B, Srinivas M, Salto´ C, Vennstro¨m B, Reh TA, Forrest D.* Nat Genet 2001;27:94 –98.
C
OLOR VISION IS FACILITATED BY DISTINCT POPULA-
tions of cone photoreceptors in the retina. In rodents, cones expressing different opsin photopigments are sensitive to middle (M, ‘green’) and short (S, ‘blue’) wavelengths, and are differentially distributed across the retina. The mechanisms that control which opsin is expressed in a particular cone are poorly understood, but previous in vitro studies implicated thyroid hormone in cone differentiation. Thyroid hormone receptor 2 (Tr2) is a ligandactivated transcription factor that is expressed in the outer nuclear layer of the embryonic retina. In this experiment the authors delete Thrb (encoding Tr2) in mice, causing the selective loss of M-cones and a concomitant increase in S-opsin immunoreactive cones. Moreover, the gradient of cone distribution is disturbed, with S-cones becoming widespread across the retina. The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Tr2 in the commitment to an M-cone identity. The authors question whether these findings raise the possibility that Thrb mutations may be associated with human cone disorders.—Thomas J. Liesegang *Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, New York, New York. E-mail: [email protected].
ABSTRACTS
689
● A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy. Zhang K, Kniazeva M, Han M, Li W, Yu Z, Yang Z, Li Y, Metzker ML, Allikmets R, Zack DJ, Kakuk LE, Lagali PS, Wong PW, MacDonald IM, Sieving PA, Figueroa DJ, Austin CP, Gould RJ, Ayyagari R, Petrukhin K.* Nat Genet 2001;27:89 –93.
S
TARGARDT-LIKE MACULAR DYSTROPHY (STGD3, MIM
600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. The authors limited the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long
VOL. 131, NO. 5
chain fatty acids. The authors feel that they are the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration. *Department of Pharmacology, Merck Research Laboratories, West Point, Pennsylvania. E-mail: [email protected].
●
A thyroid hormone receptor that is required for the development of green cone photoreceptors. Ng L, Hurley JB, Dierks B, Srinivas M, Salto´ C, Vennstro¨m B, Reh TA, Forrest D.* Nat Genet 2001;27:94 –98.
C
OLOR VISION IS FACILITATED BY DISTINCT POPULA-
tions of cone photoreceptors in the retina. In rodents, cones expressing different opsin photopigments are sensitive to middle (M, ‘green’) and short (S, ‘blue’) wavelengths, and are differentially distributed across the retina. The mechanisms that control which opsin is expressed in a particular cone are poorly understood, but previous in vitro studies implicated thyroid hormone in cone differentiation. Thyroid hormone receptor 2 (Tr2) is a ligandactivated transcription factor that is expressed in the outer nuclear layer of the embryonic retina. In this experiment the authors delete Thrb (encoding Tr2) in mice, causing the selective loss of M-cones and a concomitant increase in S-opsin immunoreactive cones. Moreover, the gradient of cone distribution is disturbed, with S-cones becoming widespread across the retina. The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Tr2 in the commitment to an M-cone identity. The authors question whether these findings raise the possibility that Thrb mutations may be associated with human cone disorders.—Thomas J. Liesegang *Department of Human Genetics, Box 1498, Mount Sinai School of Medicine, New York, New York. E-mail: [email protected].
ABSTRACTS
689