gene arrays in which the nucleotide sequences of 
the coding regions and promoter are normal. 
Retinitis Pigmentosa 
Over the past three years, Dr. Ching-Hwa Sung, 
Ms. Jennifer Macke, and Dr. Nathans have looked for 
naturally occurring mutations in the gene encoding 
human rhodopsin. Rhodopsin mediates vision in 
dim light and resides in the photoreceptors of the 
peripheral retina. Deficiencies in night and periph- 
eral vision are the hallmarks of retinitis pigmentosa 
(RP) , a heterogenous group of inherited progressive 
retinal dystrophies. In an initial survey, 13 rhodop- 
sin point mutations were identified in 39 of l6l 
families with autosomal dominant RP, and in each 
case the mutation was found to co-inherit with reti- 
nal disease. Five new mutations have recently been 
identified, and together with those found by other 
investigators, the total number of rhodopsin muta- 
tions found among RP patients is now over 40. 
To examine the biochemical properties of the de- 
fective rhodopsins. Dr. Sung, Ms. Carol Davenport, 
and Dr. Nathans have produced 34 of them in tissue 
culture cells. Most of the mutant rhodopsins appear 
to be defective in their folding and/or stability. 
These proteins accumulate in the endoplasmic retic- 
ulum and are degraded more rapidly than the wild 
type. 
A subset of the mutations cluster near rhodopsin's 
carboxyl terminus. These proteins fold correctly 
and are transported to the plasma membrane. The 
nature of their biochemical defect is currently 
under investigation. (The project described above 
was supported in part by a grant from the National 
Retinitis Pigmentosa Foundation.) 
Dr. Nathans is also Associate Professor of Molec- 
ular Biology and Genetics and of Neuroscience at 
the fohns Hopkins University School of Medicine. 
Articles 
Dhallan, R.S., Macke, J. P., Eddy, R.L., Shows, T.B., 
Reed, R.R., Yau, K.-W., and Nathans, J. 1992. 
Human rod photoreceptor cGMP-gated channel: 
amino acid sequence, gene structure, and func- 
tional expression. //Vewrosc/ 12:3248-3256. 
Jacobson, S.G., Kemp, CM., Sung, C.-H., and Na- 
thans, J. 1991. Retinal function and rhodopsin 
levels in autosomal dominant retinitis pigmentosa 
with rhodopsin mutations. Am f Ophthalmol 
112:256-271. 
Kemp, CM., Jacobson, S.G., Roman, A.J., Sung, 
C.-H., and Nathans, J. 1992. Abnormal rod adap- 
tation in autosomal dominant retinitis pigmentosa 
with proIine-23-histidine rhodopsin mutation. 
Am J Ophthalmol 113:165-174. 
Merbs, S.L., and Nathans, J. 1992. Absorption spec- 
tra of human cone pigments. Nature 356:433- 
435. 
Nathans, J. 1992. Rhodopsin: structure, function, 
and genetics. Biochemistry 31:4923-4931- 
Nathans, J., Sung, C.-H., Weitz, C.J., Davenport, 
CM., Merbs, S.L., and Wang, Y. 1992. Visual pig- 
ments and inherited variation in human vision./ 
Gen Physiol Al A 
Sung, C.-H., Schneider, B.G., Agarwal, N., Paper- 
master, D.S., and Nathans, J. 1991. Functional 
heterogeneity of mutant rhodopsins responsible 
for autosomal dominant retinitis pigmentosa. 
Proc Natl Acad Sci USA 88:8840-8844. 
Wang, S.-Z., Adler, R., and Nathans, J. 1992. A vi- 
sual pigment from chicken that resembles rho- 
dopsin: amino acid sequence, gene structure, and 
functional expression. Biochemistry 31:3309- 
3315. 
Weitz, C.J., Miyake, Y., Shinzato, K., Montag, E., 
Zrenner, E., Went, L.N., and Nathans, J. 1992. 
Human tritanopia associated with two amino acid 
substitutions in the blue-sensitive opsin. Am f 
Hum Genet 50:498-507. 
Weitz, C.J., and Nathans, J. 1992. Histidine resi- 
dues regulate the transition of photoexcited rho- 
dopsin to its active conformation, metarhodopsin 
II. Neuron 8:465-472. 
Weitz, CJ., and Nathans, J. 1992. Human tritan- 
opia associated with a third amino acid substitu- 
tion in the blue-sensitive visual pigment [letter]. 
Am f Hum Genet 51:444-446. 
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