ライフサイエンスコーパス: ABCA4

1 plasmid containing rhodopsin promoter (pRHO-ABCA4).

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

3 and other cytoplasmic and lumenal domains of ABCA4.

4 onger evidence for association with MAFB and ABCA4.

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

6 osomal recessive inheritance of mutations in ABCA4.

7 valence rates per families) were as follows: ABCA4 (20.8%), USH2A (9.1%), RPGR (5.1%), PRPH2 (4.6%),

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

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

10 , 488 nm excitation) were acquired in albino Abca4(-/-), Abca4(+/-), and Abca4(+/+) mice (ages 2-12 m

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

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

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

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

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

19 ne therapy in Abca4(-/-) mice using ECO/pRHO-ABCA4 and ECO/pRHO-ABCA4-SV40 nanoparticles induced 36%

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

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

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

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

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

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

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

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

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

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

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

31 identified pathogenic variants in the PRPH2, ABCA4, and CTNNA1 genes, which allowed reclassification

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

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

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

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

36 1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2.

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

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

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

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

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

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

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

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

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

46 Our study, conducted in the largest ABCA4-associated disease cohort reported to date, update

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

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

49 Because ABCA4-associated diseases are evolving retinal dystrophi

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

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

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

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

54 hort of patients with molecularly-confirmed, ABCA4-associated Stargardt disease (STGD1) relative to n

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

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

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

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

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

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

61 el, including a putative founder mutation in ABCA4 (c.3260A>G, p.Glu1087Gly), detected in two familie

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

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

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

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

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

67 es that cause inherited macular dystrophies (ABCA4, CTNNA1, and PRPH2).

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

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

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

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

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

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

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

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

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

77 erformed with minigene constructs containing ABCA4 exon 39.

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

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

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

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

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

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

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

85 The causative ABCA4 gene encodes a protein localizing to photoreceptor

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

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

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

89 The ABCA4 gene was analyzed by deep sequencing technology us

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

91 The ABCA4 gene was screened for mutations.

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

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

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

95 atients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperi

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

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

98 1, MIM 248200) is caused by mutations in the ABCA4 gene.

99 ossible large deletions or insertions in the ABCA4 gene.

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

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

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

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

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

105 gnosis and proven pathogenic variants in the ABCA4 gene.

106 STGD is caused by mutations in ABCA4 gene.

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

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

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

110 ameliorate clinical symptoms resulting from ABCA4 genetic defects.

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

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

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

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

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

116 Complete sequencing of ABCA4 in STGD patients identifies compound heterozygous

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

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

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

120 t significantly lowered RBP4 serum levels in Abca4(-/-) knockout mice with concomitant normalization

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

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

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

124 possibly reside in noncoding regions of the ABCA4 locus.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

144 Subretinal gene therapy in Abca4(-/-) mice using ECO/pRHO-ABCA4 and ECO/pRHO-ABCA4-

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

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

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

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

149 4(-/-) mice was milder than that in Rdh8(-/-)Abca4(-/-) mice, and a 2-fold increased TLR3 expression

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

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

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

153 TGD1-like patient and blue light-illuminated Abca4(-/-) mice, lipofuscin and melanolipofuscin granule

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

155 In Abca4(-/-) mice, the acute blue light diminished the mea

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

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

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

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

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

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

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

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

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

165 95% CI 0.635-0.778, P = 1.44 x 10(-11); and ABCA4, most significant SNP rs560426, with OR = 1.432, 9

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

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

168 This blue light-illuminated pigmented Abca4(-/-) mouse model presented retinal pigment epithel

169 The pigmented Abca4(-/-) mouse strain only reflects the early stage of

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

186 ABCA4 mutations were identified in 22 patients, who tend

187 with the CRD phenotype often associated with ABCA4 mutations.

188 as inherited retinal dystrophy, is caused by ABCA4 mutations.

189 he spectrum of retinal dystrophies caused by ABCA4 mutations.

190 finding (n = 105 [45%]) and associated with ABCA4 (n = 73 [70%]), PRPH2 (n = 9 [9%]), CERKL (n = 3 [

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

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

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

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

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

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

197 t pathogenic variants were identified in 506 ABCA4 patients, 50 of which were novel.

198 -sensitive amino lipid ECO and a therapeutic ABCA4 plasmid containing rhodopsin promoter (pRHO-ABCA4)

199 In this study, we modified the ABCA4 plasmid with simian virus 40 enhancer (SV40, pRHO-

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

201 According to our observations, patients with ABCA4 presenting with 2 truncating variants may first pr

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

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

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

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

206 Mutant ABCA4 proteins expressed heterologously in mammalian cel

207 For various genes including ABCA4, PRPH2, CDHR1, and PROM1, higher qAF(8) measures w

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

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

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

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

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

213 ht-induced retinal degeneration mouse model (Abca4 (-/-) Rdh8 (-/-)), raloxifene (a benzothiophene-ty

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

237 A total of 77 patients with ABCA4-related retinopathy and 110 control subjects under

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

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

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

241 12, and the ATP-binding cassette transporter Abca4, retinoid cycle enzymes involved in all-trans-reti

242 l disease and clinical features atypical for ABCA4 retinopathy.

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

244 pectrum of clinical features consistent with ABCA4 retinopathy.

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

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

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

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

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

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

251 ified nine pathogenic variants in six genes (ABCA4, RPE65, MERTK, USH2A, SPATA7, TULP1) in 10 consang

252 ABCA4 sequence changes were identified in 85 patients fr

253 Three ABCA4 sequence variations identified exclusively in Afri

254 Three ABCA4 sequence variations were identified exclusively in

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

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

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

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

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

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

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

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

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

264 at ECO formed stable nanoparticles with pRHO-ABCA4-SV40 in the presence of sucrose, but not with sorb

265 (-/-) mice using ECO/pRHO-ABCA4 and ECO/pRHO-ABCA4-SV40 nanoparticles induced 36% and 29% reduction i

266 troduction of SV40 enhancer for plasmid pCMV-ABCA4-SV40 with a CMV promoter.

267 id with simian virus 40 enhancer (SV40, pRHO-ABCA4-SV40) for enhanced gene expression.

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

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

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

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

272 In contrast, ABCA4 transported phosphatidylethanolamine in the revers

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

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

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

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

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

278 Analysis of the most prevalent ABCA4 variant in Spain, c.3386G>T; p.(Arg1129Leu), revea

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

280 % of patients (n = 5), a single heterozygous ABCA4 variant was identified; all these participants had

281 e compared with those with at least 1 milder ABCA4 variant.

282 the genotype-phenotype model established for ABCA4 variants and broadens the mutational spectrum of t

283 etween siblings with STGD1 carrying the same ABCA4 variants is a prevalent phenomenon.

284 We characterized 506 patients with ABCA4 variants using conventional genetic tools and next

285 ion of lipofuscin depends on the severity of ABCA4 variants, precedes other structural changes, and m

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