ライフサイエンスコーパス: ABCA4

1 st for mutations in known arRP genes and not ABCA4.

2 and other cytoplasmic and lumenal domains of ABCA4.

3 osomal recessive inheritance of mutations in ABCA4.

4 onger evidence for association with MAFB and ABCA4.

5 clearance is achieved by all-trans-RDHs and Abca4.

6 Mutations in ABCA4, a member of the ATP-binding cassette (ABC) family

7 disease caused by mutations in the gene for ABCA4, a transporter in photoreceptor outer segments (OS

8 , 488 nm excitation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 m

9 oxy-A2E in aged human RPE and in eye cups of Abca4/Abcr-/- mice, a model of Stargardt disease.

10 r-specific ATP-binding cassette transporter (ABCA4) accelerate the dark adaptation of cones, first, d

11 tated in the present cohort were CACNA1F and ABCA4, accounting for 14.9% (n = 10) and 11.9% (n = 8) o

12 that this variant results in the absence of ABCA4 activity.

13 Rdh8, Rdh12, and Abca4 all protect the retina and reduce A2E production b

14 verity metric and contributions made by each ABCA4 allele were predicted.

15 owever, the frequency of possibly pathogenic ABCA4 alleles in arRP families was only slightly higher

16 An increasing understanding of causal ABCA4 alleles in arSTGD and arCRD facilitates disease di

17 dodominant inheritance and the presence of 3 ABCA4 alleles within the family.

18 In 66 individuals with known disease-causing ABCA4 alleles, we defined retina-wide disease expression

19 ABCA4, also called ABCR, is a retinal-specific member of

20 ->C was found to span approximately 96 kb of ABCA4 and did not contain other rare sequence variants.

21 g for mutations in candidate genes including ABCA4 and PRPH2, DNA from 3 members of the family, inclu

22 The results suggest a possible role of ABCA4 and, in particular, the NBD1 domain in 11-cis-reti

23 itation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with

24 nth-old mice with and without Atg7 from both Abca4(-/-) and Abca4(+/+) backgrounds.

25 RNA sequencing of WT, Abca4(-/-) and Abca4(PV/PV) mice revealed mild gene expr

26 Abca4(-/-) and Rdh8(-/-)/Abca4(-/-) mice that are models

27 Rdh8(-/-)Abca4(-/-) and Rdh8(-/-)Rdh12(-/-)Abca4(-/-) mice displa

28 d increases, and the fold difference between Abca4(-/-) and wild-type mice was more pronounced (appro

29 (I-C) induced retinal cell death in Rdh8(-/-)Abca4(-/-) and WT mice both in vivo and ex vivo, this wa

30 both the ATP-binding cassette transporter 4 (Abca4) and enzyme retinol dehydrogenase 8 (Rdh8), protei

31 of both ATP-binding cassette transporter 4 (Abca4) and retinol dehydrogenase 8 (Rdh8) activities.

32 lacking ATP-binding cassette transporter 4 (ABCA4) and retinol dehydrogenase 8 (RDH8), proteins crit

33 tween the frog ABCA4s, annotated T. rubripes ABCA4, and mammalian ABCA4 proteins was carried out.

34 cumulation of lipofuscin bisretinoids in the Abca4(-/-) animal model.

35 tions in the photoreceptor-specific flippase ABCA4 are associated with Stargardt disease and many oth

36 ABCA1, ABCA7, and ABCA4 are members of the ABCA subfamily of ATP-binding c

37 Mutations in ABCA4 are responsible for several recessive macular dyst

38 Mutations in ABCA4 are responsible for Stargardt disease, a degenerat

39 1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2.

40 similar for isolated CLO and CLP, except for ABCA4-ARHGAP29.

41 Although the ABCA4 array remains a good first-pass screening option,

42 ether all-trans retinol formation depends on Abca4, arrestin, rhodopsin kinase, and the palmitylation

43 rods derived from 129/sv wild-type mice and Abca4-, arrestin-, and rhodopsin kinase-deficient mice a

44 he secondary structure of the ECD2 domain of ABCA4, as well as in its interaction with all-trans-reti

45 role of the ATP-binding cassette transporter ABCA4 associated with Stargardt macular degeneration and

46 The qAF method can differentiate between ABCA4-associated and non-ABCA4-associated BEM and may gu

47 rkers that can aid in the differentiation of ABCA4-associated and non-ABCA4-associated disease.

48 fferentiate between ABCA4-associated and non-ABCA4-associated BEM and may guide clinical diagnosis an

49 Gene replacement is a logical strategy for ABCA4-associated disease, particularly given the current

50 ine natural history or outcome of therapy in ABCA4-associated disease.

51 differentiation of ABCA4-associated and non-ABCA4-associated disease.

52 Because ABCA4-associated diseases are evolving retinal dystrophi

53 gardt disease, cone-rod dystrophy, and other ABCA4-associated phenotypes were prescreened for mutatio

54 ion in homozygosity in a patient cohort with ABCA4-associated phenotypes.

55 Patients (n = 38) with ABCA4-associated retinal degeneration (RD) or with retin

56 t (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and th

57 dt lies at the severe end of the spectrum of ABCA4-associated retinal phenotypes.

58 trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (ret

59 Human RPE/choroid, eyes harvested from Abca4 (ATP-binding cassette transporter 4) null mutant m

60 ore abundant in mice with a null mutation in Abca4 (ATP-binding cassette transporter 4), the gene cau

61 th and without Atg7 from both Abca4(-/-) and Abca4(+/+) backgrounds.

62 n of an RPE-specific protein was observed in Abca4(-/-) but not in wild-type mice under the same cond

63 uch as rhodopsin, Peripherin-rds, Rom-1, and Abca4, but significantly disrupts the localization of th

64 n and was driven by three common variants in ABCA4 (c.5682G > C, c.5814A > G, c.5844A > G), all confe

65 strains and disease models (129S2, C57Bl/6, Abca4(-/-), C3H-Pde6b(rd1/rd1), Rho(-/-), and BALB/c mic

66 Here we show that ABCA4 can transport N-11-cis-retinylidene-phosphatidylet

67 Other mutant alleles of ABCA4 cause the related diseases, recessive cone-rod dys

68 However, the large size of the ABCA4 cDNA (6.8 kbp) has hampered progress in the develo

69 The ABCA4, CNGB3, KCNV2, PDE6C, and RPGR genes were analyzed

70 n of toxic bisretinoid compounds as found in ABCA4-deficient mice and individuals with Stargardt macu

71 We report that young adult RDH8/ABCA4-deficient mice have normal M-cone morphology but r

72 technology to subretinally deliver ABCA4 to Abca4-deficient mice.

73 by the RPE due to its slow release from RDH8/ABCA4-deficient rods.

74 ilitate the discovery of factors that modify ABCA4 disease and will also aid in the optimal selection

75 Patients were enrolled from the ABCA4 disease database at Columbia University or by inqu

76 MP is strongly affected by the stage of ABCA4 disease leading to abnormal foveal architecture.

77 ent with the range of phenotypes observed in ABCA4 disease.

78 ppropriate candidates for clinical trials in ABCA4 disease.

79 All individuals with ABCA4-disease show macular degeneration, but only some a

80 etically engineered to lack Rdh8, Rdh12, and Abca4, either singly or in various combinations, were in

81 use models to date are based on knockouts of Abca4, even though the disease is often caused by missen

82 erformed with minigene constructs containing ABCA4 exon 39.

83 equenced in 114 STGD patients with one known ABCA4 exonic mutation revealing, on average, 200 introni

84 flammatory changes were observed in Rdh8(-/-)Abca4(-/-) eyes by RNA expression analysis.

85 Mutations in the ABCA4 gene and early onset of disease were independent p

86 ne harboring disease-causing variants in the ABCA4 gene and with specified ocular lesions were enroll

87 Mutations in the ABCA4 gene are a common cause of autosomal recessive ret

88 Mutations in the photoreceptor-specific ABCA4 gene are associated with several inherited retinal

89 retinal diseases caused by mutations in the ABCA4 gene are being considered for gene replacement the

90 Loss-of-function mutations in the ABCA4 gene are responsible for a subset of recessive ret

91 any mutations in the coding sequences of the ABCA4 gene are still unknown, and many possibly reside i

92 sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level

93 The causative ABCA4 gene encodes a protein localizing to photoreceptor

94 c.5461-10T-->C and sequence analysis of the ABCA4 gene for a homozygous proband.

95 Mice with a knockout mutation in the abca4 gene massively accumulate toxic lipofuscin pigment

96 STGD patients with genetically confirmed ABCA4 gene mutations seen at the Wilmer Eye Institute wi

97 The entire ABCA4 gene open reading frame, including all exons and f

98 The ABCA4 gene was analyzed by deep sequencing technology us

99 Analysis of the ABCA4 gene was performed using microarray analysis, sequ

100 The ABCA4 gene was screened for mutations.

101 In the fraction of the cohort where the ABCA4 gene was sequenced completely, the detection rates

102 r suspected disease-causing mutations in the ABCA4 gene were included.

103 After complete sequencing of the ABCA4 gene with negative results, the screening for dise

104 ficant association of common variants in the ABCA4 gene with retinal disease, assessed by a score-bas

105 pathogenicity of the G1961E mutation in the ABCA4 gene, and present the range of retinal phenotypes

106 donor's DNA identified two mutations in the ABCA4 gene, IVS14+1G > C and Phe1440del1 cT, each on a s

107 gnosis and proven pathogenic variants in the ABCA4 gene.

108 1, MIM 248200) is caused by mutations in the ABCA4 gene.

109 ossible large deletions or insertions in the ABCA4 gene.

110 uman donor with ARRP due to mutations in the ABCA4 gene.

111 gous or homozygous, variants detected in the ABCA4 gene.

112 re coding region and the splice sites of the ABCA4 gene.

113 least one disease-associated variant of the ABCA4 gene.

114 ople and results from genetic defects in the ABCA4 gene.

115 netic variants in the coding sequence of the ABCA4 gene.

116 (ATP)-binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enro

117 We have identified ABCA4 genes from African (Xenopus laevis) and Western (S

118 The coding sequences of the RDS, RHO, and ABCA4 genes were screened for disease-causing mutations.

119 ameliorate clinical symptoms resulting from ABCA4 genetic defects.

120 The entire 140 kb ABCA4 genomic locus was sequenced in 114 STGD patients w

121 urrently not predictable if or when specific ABCA4 genotypes will show extramacular disease, and how

122 stive CAC loci (chr9p21, COL4A1, ATP2B1, and ABCA4) had significant associations with MI, consistent

123 with a recent report on the in vivo role of ABCA4 in 11-cis-retinal transport.

124 e mechanisms: direct involvement of RDH8 and ABCA4 in cone chromophore processing, and an indirect ef

125 ate the pathogenicity of specific alleles of ABCA4 in patients with retinal phenotypes ranging from S

126 Complete sequencing of ABCA4 in STGD patients identifies compound heterozygous

127 specific ATP-binding cassette transporter 4 (ABCA4), in dark adaptation of mammalian cones.

128 purified and reconstituted ABCA1, ABCA7, and ABCA4 into liposomes for fluorescent-lipid transport stu

129 ific ATP-binding cassette (ABC) transporter, ABCA4, is essential for transport of all-trans-retinal f

130 Lysosomal pH is elevated in RPE cells from ABCA4 knockout mice and in cultured human ARPE-19 cells

131 The sequence variability in the ABCA4 locus is extensive and the non-coding sequences do

132 Defining disease-associated alleles in the ABCA4 locus requires exceptionally well characterized la

133 possibly reside in noncoding regions of the ABCA4 locus.

134 ggesting that it is a very rare event in the ABCA4 locus.

135 The physiological role of Abca4 may include the translocation of 11-cis-retinal co

136 quired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 months) with a confocal scann

137 ely 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and approximately 20% higher in heterozy

138 The lysosomal pH of fresh RPE cells from ABCA4(-/-) mice and of chemically compromised RPE cells

139 vely and qualitatively analyzed in pigmented Abca4(-/-) mice and wild type (WT) controls in vivo.

140 (-/-) Abca4(-/-) mice compared with Rdh8(-/-)Abca4(-/-) mice at 3 and 6 months of age, indicating tha

141 ncreased 10- to 12-fold in 6- to 9-month-old Abca4(-/-) mice compared with controls, while 488 nm AF

142 ted in light-illuminated retinas of Rdh8(-/-)Abca4(-/-) mice compared with nonilluminated retinas.

143 l cells were exhibited by Tlr3(-/-)Rdh8(-/-) Abca4(-/-) mice compared with Rdh8(-/-)Abca4(-/-) mice a

144 The decline in A2E levels in the Abca4(-/-) mice corresponded to reduced photoreceptor ce

145 eveloped CORD, 6-month-old Tlr3(-/-)Rdh8(-/-)Abca4(-/-) mice did not evidence an abnormal retinal phe

146 Rdh8(-/-)Abca4(-/-) and Rdh8(-/-)Rdh12(-/-)Abca4(-/-) mice displayed slowly progressive, severe ret

147 al and morphologic analysis in wild-type and abca4(-/-) mice fed the vitamin A-supplemented diet.

148 Sirolimus treatment of 6-month-old Rdh8(-/-)Abca4(-/-) mice for 4 months prevented choroidal neovasc

149 d in 11-month-old albino, but not pigmented, abca4(-/-) mice on both diets.

150 s-retinal dimer-PE) also decreases in albino Abca4(-/-) mice reared in cyclic light compared with dar

151 In albino Abca4(-/-) mice receiving a diet supplemented with the a

152 Old Abca4(-/-) mice revealed a flecked fundus AF pattern at

153 ng of cryostat-sectioned eyes harvested from Abca4(-/-) mice revealed that carbonyl adduct deposition

154 qAF was approximately 2-fold higher in Abca4(-/-) mice than in Abca4(+/+) mice and approximatel

155 Abca4(-/-) and Rdh8(-/-)/Abca4(-/-) mice that are models of accelerated bisretino

156 Unlike 3-month-old Rdh8(-/-)Abca4(-/-) mice that developed CORD, 6-month-old Tlr3(-/

157 ed retinal degeneration in Tlr3(-/-)Rdh8(-/-)Abca4(-/-) mice was milder than that in Rdh8(-/-)Abca4(-

158 Wild-type and abca4(-/-) mice were fed normal or vitamin A-supplemente

159 h age in mouse eyes and was more abundant in Abca4(-/-) mice, a model of recessive Stargardt disease.

160 ficacy of potential therapeutics in Rdh8(-/-)Abca4(-/-) mice, a rodent model of human age-related mac

161 Similar to Abca4(-/-) mice, Abca4(PV/PV) mice showed substantial A2

162 4(-/-) mice was milder than that in Rdh8(-/-)Abca4(-/-) mice, and a 2-fold increased TLR3 expression

163 ounced lipofuscin accumulation in the RPE of Abca4(-/-) mice, ERG and histology showed a slow age-rel

164 In contrast to RPE cells in abca4(-/-) mice, human RPE cells exposed to abca4(-/-) r

165 induced mitochondrial injury in vitro and in Abca4(-/-) mice, indicating that they could be effective

166 In Abca4(-/-) mice, lipofuscin-related 488 nm AF increased

167 scin bisretinoid formation in the retinas of Abca4(-/-) mice.

168 -CRRY) into the subretinal space of 4-wk-old Abca4(-/-) mice.

169 normal visual cycle, and high in BALB/c and Abca4(-/-) mice.

170 enuated degenerative retinopathy in Rdh8(-/-)Abca4(-/-) mice.

171 was detected by SD-OCT in Rdh8(-/-)Rdh12(-/-)Abca4(-/-) mice.

172 A2E amounts were found in Rdh8(-/-)Rdh12(-/-)Abca4(-/-) mice.

173 y accelerate lipofuscin pigment formation in abca4(-/-) mice.

174 in retina and retinal pigment epithelium of abca4(-/-) mice.

175 t metabolizes MG and GO were up-regulated in Abca4(-/-) mice.

176 Administration of HPR to ABCA4-/- mice caused immediate, dose-dependent reduction

177 nthesis, HPR was chronically administered to ABCA4-/- mice.

178 prescreened for mutations in ABCA4 with the ABCA4 microarray, resulting in finding 1 of 2 expected m

179 s suggests the existence of at least two non-ABCA4 modifying factors.

180 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 9

181 Using the abca4(-/-) mouse model for recessive Stargardt, we inves

182 r NTPDase1 was raised in RPE tissue from the ABCA4(-/-) mouse model of Stargardt's retinal degenerati

183 ty of all-trans-retinal, for instance in the Abca4(-/-) mouse, are discussed.

184 described murine model of AMD, the Rdh8(-/-)Abca4(-/-) mouse.

185 as VX-809, can rescue the processing of the ABCA4 mutants, particularly their expression at the cell

186 field data, and 92 patients with identified ABCA4 mutations (46 with 1 mutation, and 47 with 2 or mo

187 age, 21.9+/-8.3 years) than patients without ABCA4 mutations (mean age, 42.1+/-14.9 years).

188 ates in retinas of mice and humans harboring ABCA4 mutations and was proposed to be a precursor of A2

189 eptors are more severely affected than rods; ABCA4 mutations are the most common cause of this hetero

190 ABCA4 mutations as well as age of onset <20 years were s

191 refining our understanding of how individual ABCA4 mutations contribute to phenotype.

192 netic screening of 44 patients revealed >/=2 ABCA4 mutations in 37 patients and single heterozygous m

193 we detected 70.5% and 36.6% of all expected ABCA4 mutations in arSTGD and arCRD patient cohorts, res

194 The pathologic steps by which ABCA4 mutations lead to clinically detectable retinal pi

195 We suggest that ABCA4 mutations may be associated with a retinitis pigme

196 mentation should be avoided in patients with ABCA4 mutations or other retinal or macular dystrophies

197 All patients were screened for ABCA4 mutations using the ABCR600 microarray, next-gener

198 Although no ABCA4 mutations were detected in either patient, whole-e

199 ABCA4 mutations were found in 8 of 90 (9%) of AR-CD, and

200 ABCA4 mutations were identified in 22 patients, who tend

201 he spectrum of retinal dystrophies caused by ABCA4 mutations.

202 with the CRD phenotype often associated with ABCA4 mutations.

203 Conversely, in the ABCA4-negative group, 22 of 26 eyes (13 of 15 patients)

204 o the subretinal space of 4-5-day-old albino Abca4 null mutant and Abca4 wild-type mice.

205 eline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 center

206 ment activation following exposure to either Abca4(-/-) or wild-type OS.

207 ck complex deposition following ingestion of Abca4(-/-) OS.

208 following exposure to bisretinoid-containing Abca4(-/-) OS.

209 In the ABCA4-positive group, 37 of 41 eyes (19 of 22 patients)

210 ter progenitors were combined to form a full ABCA4 progenitor in ancestral chordates.

211 aled that it leads to mRNA exon skipping and ABCA4 protein truncation.

212 , surprisingly, only trace amounts of mutant ABCA4 protein were noted in the retina.

213 a-specific ATP binding cassette transporter, ABCA4 protein, is associated with a broad range of inher

214 hosphate (ATP)-binding cassette transporter (ABCA4) protein that is mutated in Stargardt disease (STG

215 Mutant ABCA4 proteins expressed heterologously in mammalian cel

216 , annotated T. rubripes ABCA4, and mammalian ABCA4 proteins was carried out.

217 We generated Abca4(PV/PV) knock-in mice homozygous for the complex PV

218 RNA sequencing of WT, Abca4(-/-) and Abca4(PV/PV) mice revealed mild gene expression alterati

219 Similar to Abca4(-/-) mice, Abca4(PV/PV) mice showed substantial A2E and lipofuscin

220 ease-causing mutations in the NBD1 region of ABCA4, R1108C, and R1129C, which occur within regions of

221 As a group, patients with ABCA4-RD had reduced foveal MPOD, and there was a strong

222 Macular function in ABCA4-RD patients transitioned from lower sensitivity at

223 with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplemen

224 re significantly increased in the retinas of Abca4(-/-)Rdh8(-/-) mice after light exposure, suggestin

225 le of CCL3 in retinal degeneration, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice and Ccl3(-/-)Mertk(-/-) mice we

226 r retinal inflammation and degeneration than Abca4(-/-)Rdh8(-/-) mice did in age-related chronic reti

227 Tlr4(-/-)Abca4(-/-)Rdh8(-/-) mice displayed milder retinal degene

228 Following intense light exposure, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice displayed persistent retinal in

229 In contrast, Ccl3(-/-)Abca4(-/-)Rdh8(-/-) mice exhibited a milder retinal infl

230 Abca4(-/-)Rdh8(-/-) mice featuring defective atRAL clear

231 Here we report that bright light exposure of Abca4(-/-)Rdh8(-/-) mice increased atRAL levels in the r

232 Analysis of the eyes of Abca4(-/-)Rdh8(-/-) mice that display light-induced reti

233 Exposure of Cx3Cr1(gfp/Delta)Abca4(-/-)Rdh8(-/-) mice to intense light resulted in th

234 Abca4(-/-)Rdh8(-/-) mice, which mimic many features of h

235 response to light illumination in retinas of Abca4(-/-)Rdh8(-/-) mice, which showed delayed clearance

236 milder retinal degenerative phenotypes than Abca4(-/-)Rdh8(-/-) mice.

237 light-induced photoreceptor degeneration of Abca4(-/-)Rdh8(-/-) mice.

238 er levels of prostaglandin G2 in the eyes of Abca4(-/-)Rdh8(-/-) mice.

239 and increased Ccl4 expression compared with Abca4(-/-)Rdh8(-/-) mice.

240 f Ccl3 (MIP-1a) 24 h after light exposure in Abca4(-/-)Rdh8(-/-) mice.

241 y, we examined the role of chemokines in the Abca4(-/-)Rdh8(-/-) mouse model of Stargardt disease and

242 3)R) receptors and found they both protected Abca4(-/-)Rdh8(-/-) mouse retinas from light-induced deg

243 tinoid-derived fluorescence and expansion of Abca4(-/-)Rdh8(-/-) mouse rod cell outer segments accomp

244 E cell cultures and of eyecups obtained from Abca4-Rdh8 double knock-out (DKO) mice, respectively.

245 ATP-binding cassette, subfamily A, member 4 (ABCA4)-related retinopathy, is a genetic condition chara

246 sed and drug therapies that aim to alleviate ABCA4-related retinal disease.

247 Homozygous G1961E mutation in ABCA4 results in a range of retinal pathology.

248 y prevented atrophic changes in the Rdh8(-/-)Abca4(-/-) retina with retinylamine demonstrating the gr

249 avelength fluorescence emission intrinsic to abca4(-/-) retinal explants is shown to emanate from A2P

250 ls with rod outer segments from wild-type or abca4(-/-) retinas.

251 12, and the ATP-binding cassette transporter Abca4, retinoid cycle enzymes involved in all-trans-reti

252 l disease and clinical features atypical for ABCA4 retinopathy.

253 here may be more than 1 disease mechanism in ABCA4 retinopathy.

254 pectrum of clinical features consistent with ABCA4 retinopathy.

255 Neither the activities of Abca4, rhodopsin kinase, and arrestin, nor the palmityla

256 Mutant ABCA4 RNA levels approximated WT ABCA4 RNA levels but, s

257 Mutant ABCA4 RNA levels approximated WT ABCA4 RNA levels but, surprisingly, only trace amounts o

258 abca4(-/-) mice, human RPE cells exposed to abca4(-/-) rod outer segments adaptively increased expre

259 levels of complement-activation products in abca4(-/-) RPE cells.

260 ximal beta-HB production was observed in the Abca4(-/-) RPE, in which loss of the ATP-binding cassett

261 However, the understanding of ABCA4's role in the visual cycle is limited due to the l

262 ABCA4 sequence changes were identified in 85 patients fr

263 Three ABCA4 sequence variations identified exclusively in Afri

264 Three ABCA4 sequence variations were identified exclusively in

265 atients, 10 unrelated patients shared 1 of 3 ABCA4 sequence variations: c.3602T>G (p.L1201R); c.3899G

266 minor alleles of common genetic variants in ABCA4 significantly reduce susceptibility to develop tox

267 autofluorescence (UWF-FAF) in patients with ABCA4 Stargardt disease (STGD) and correlate these data

268 ABCA1 Tangier mutants and the corresponding ABCA4 Stargardt mutants showed significantly reduced pho

269 d to the retinal pigment epithelium (RPE) in Abca4 (-/-) Stargardt model mice compared to their relev

270 sing polarized primary RPE and the pigmented Abca4(-/-) Stargardt disease mouse model, we provide evi

271 STGD1 patients and Abca4(-/-) (STGD1) mice exhibit buildup of bisretinoid-c

272 nts and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 micro

273 Notably, the deletion of RDH8 and ABCA4 suppressed the dark adaptation of M-cones driven b

274 with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57B

275 Following mutation screening of ABCA4, the molecular findings were compared with those o

276 ed DNA NP technology to subretinally deliver ABCA4 to Abca4-deficient mice.

277 We detected persistent ABCA4 transgene expression for up to 8 months after inje

278 In contrast, ABCA4 transported phosphatidylethanolamine in the revers

279 ) is caused by mutations in the gene for the ABCA4 transporter in photoreceptor outer segments.

280 disease caused by dysfunction or loss of the ABCA4 transporter in rods and cones.

281 The frequent ABCA4 variant c.5461-10T-->C has a subtle effect on spli

282 The ABCA4 variant c.5461-10T-->C is located on a founder hap

283 We found a single heterozygous ABCA4 variant in 11 patients (52%), 2 compound heterozyg

284 At least 1 disease-causing ABCA4 variant was identified in 47 patients.

285 % of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had

286 suggested 12 new likely pathogenic intronic ABCA4 variants, some of which were specific to (isolated

287 This phenotype may be caused by 1 or 2 ABCA4 variants.

288 notypes linked to the presence of additional ABCA4 variants.

289 atively high carrier frequency of pathogenic ABCA4 variants.

290 designed to find the missing disease-causing ABCA4 variation by a combination of next-generation sequ

291 products of lipid peroxidation in eyes from abca4(-/-) versus wild-type mice.

292 tack by the complement system, were lower in abca4(-/-) versus wild-type RPE.

293 ar degeneration (AMD) in humans, deletion of Abca4 was introduced into Atg7(flox/flox);VMD2-rtTA-cre+

294 Molecular screening of ABCA4 was undertaken.

295 cid sequences of the four soluble domains of ABCA4, we demonstrated that the nucleotide binding domai

296 transport and ATPase activities of ABCA1 and ABCA4 were reduced by 25% in the presence of 20% cholest

297 Mutations in ABCA4 were the most common cause of disease in this coho

298 of 4-5-day-old albino Abca4 null mutant and Abca4 wild-type mice.

299 d the interactions of the soluble domains of ABCA4 with both 11-cis- and all-trans-retinal.

300 phenotypes were prescreened for mutations in ABCA4 with the ABCA4 microarray, resulting in finding 1