Table 2.

Animal models of human eye diseases associated with defective metabolism of visual retinoids

Gene Name	Animal Model	Phenotype	Ref.
Retinal-specific ATP-binding cassette transporter member 4 (ABCA4)	abcr−/− mice	The two lines of abcr−/− mice exhibit accumulation of high levels of lipofuscin within the RPE cells; increased levels of retinal in the outer segment (OS) and delayed dark adaptation	(9, 210)
Lecithin: retinal acyltransferase (LRAT)	lrat−/− mice	The lrat−/− mice have no detectable levels of retinyl esters within the RPE and show severely attenuated rod and cone visual responses. Other tissues such as liver, kidney, and lung have trace levels of retinyl esters, but there are increased levels of retinyl esters in adipose tissue. A second line of lrat−/− mice that have the Neo cassette removed following recombination show a similar phenotype	(39, 40, 221)
RPE-specific protein 65 kDa; Rpe65	rpe65−/− mice	The rpe65−/− mice show severely attenuated rod and cone responses, progressive retinal degeneration owing to block in regeneration of 11-cis-RAL, consistent with the role of Rpe65 in the isomerization of all-trans-ROL. High levels of all-trans-retinyl esters accumulate in lipid vacuoles in the RPE of rpe65−/− mice	(88)
	rd12 mice	The rd12 mice have a naturally occurring nonsense mutation in exon 3 of murine Rpe65. There are no detectable levels of 11-cis-RAL or rhodopsin and lipid droplets accumulate in the RPE. At 5 months of age, small white dots appear on the retinas of rd12 mice	(123)
	Swedish Briard/Briard Beagle dogs with naturally occurring mutation	A homozygous 4bp deletion in exon 5 of canine Rpe65 leads to a frameshift mutation and truncation of the resulting polypeptide. These dogs exhibit early onset, progressive retinal dystrophy and accumulation of lipid vacuoles in their RPE	(105, 106)
Retinal G protein–coupled receptor; RG	rgr−/− mice	The rgr−/− mice have reduced levels of 11-cis-RAL and rhodopsin, and slightly reduced electroretinographic (ERG) responses. The rates of rhodopsin regeneration are similar to WT mice	(94, 95)
Retinal-binding protein 1, RLBP1	rlbp1−/− mice	rlbp1−/− mice have delayed rates of rhodopsin regeneration and recovery of chromophore following a bleach and accumulation of retinyl esters	(140)
11-cis-ROL dehydrogenase (RDH); RDH5	rdh5−/− mice	The rdh5−/− mice exhibit accumulation of cis-retinyl esters in their RPE. In contrast to the human disease caused by mutations in RDH5, fundus albipunctatus, the rdh5−/− mice do not exhibit delayed dark adaptation or the formation of the characteristic white dots	(144)