Elovl4 mRNA distribution in the developing mouse retina and phylogenetic conservation of Elovl4 genes.
OBJECTIVE
Stargardt-like macular dystrophy (STGD3) is an autosomal dominant form of early onset macular degeneration. The disease causing gene ELOVL4 encodes a protein that belongs to a family of proteins functioning in elongation of long chain fatty acids. The purpose of this study is to characterize cross-species conservation of ELOVL4 and investigate its mRNA distribution in the developing mouse eye.


METHODS
Bovine and porcine orthologs of the human ELOVL4 gene were cloned using RT-PCR method. EST and HTGS databases were searched for orthologs of ELOVL4. Cross-species alignments were performed using ClustalW. In situ hybridizations using murine Elovl4 probes were performed on frozen sections of mouse eyes.


RESULTS
Elovl4 orthologs from mammalian to invertebrate species share strong sequence homology with human ELOVL4 at the amino acid level, suggesting functional conservation of Elovl4 during evolution. Expression of Elovl4 in mouse retina begins at E15 during embryogenesis and persists in postnatal stages. However, Elovl4 is predominantly expressed in the retinal ganglion cells at P1-P3, followed by predominant expression in the outer nuclear layer at P7, with its final expression enriched in inner segments of photoreceptors.


CONCLUSIONS
Elovl4 expression in developing retina follows a dynamic pattern. It switches from predominant ganglion cell expression in embryonic and early postnatal development to predominant expression in the photoreceptor inner segments in later stages. Phylogenetic analysis reveals strong conservation of Elovl4 among different species throughout the vertebrate subphylum consistent with our hypothesis that ELOVL4 performs a fundamentally important function.
Zhang
Xian-Mei
XM
Department of Ophthalmology and Jules Stein Eye Institute, UCLA School of Medicine, USA.
Yang
Zhenglin
Z
Karan
Goutam
G
Hashimoto
Takao
T
Baehr
Wolfgang
W
Yang
Xian-Jie
XJ
Zhang
Kang
K
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003001:Cloning, Molecular; D005136:Eye Proteins / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism*; D012160:Retina / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013552:Swine
C418975:ELOVL4 protein, human; C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger