TY - JOUR
T1 - Identification of the mouse and rat orthologs of the gene mutated in Usher syndrome type IIA and the cellular source of USH2A mRNA in retina, a target tissue of the disease
AU - Huang, Dali
AU - Eudy, James D.
AU - Uzvolgyi, Eva
AU - Davis, Jack R.
AU - Talmadge, Catherine B.
AU - Pretto, Dalyir
AU - Weston, Michael D.
AU - Lehman, Janae E.
AU - Zhou, Ming
AU - Seemayer, Thomas A.
AU - Ahmad, Iqbal
AU - Kimberling, William J.
AU - Sumegi, Janos
N1 - Funding Information:
We thank Michael Danciger and Debora B. Farber (Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA) for DNA sequences used to design the forward primer used in cloning the cDNA clone M2; Donald J. Zack (The Wilmer Institute, The Johns Hopkins University School of Medicine, Baltimore, MD) for the murine retina λ-ZAP library; Constance L. Cepko (Howard Hughes Medical Institute and Department of Genetics, Harvard Medical School, Boston, MA) for a murine retina cDNA library in the pcDNAI vector; Carolyn D. Oliver for secretarial assistance; and Joe Edward for the artwork. This work was supported by NIH/NIDCD PO1 DC01813-07 and NIH/NIDCD 1R01DC03162-01A2 grants.
PY - 2002
Y1 - 2002
N2 - Usher syndrome type IIA (MIM: 27601) is an autosomal recessive disorder characterized by moderate to severe congenital deafness and progressive retinitis pigmentosa. We recently identified the human Usher syndrome type IIA gene (USH2A) on chromosome 1q41, which encodes a protein possessing 10 laminin epidermal growth factor and four fibronectin type 3 domains, both commonly observed in extracellular matrix proteins. To gain insight into the pathogenesis of Usher syndrome type IIA, we isolated and characterized the murine (Ush2a) and rat (ratUsh2a) orthologs of human USH2A. We mapped mouseUsh2a by fluorescence in situ hybridization to mouse chromosome 1 in the region syntenic to human chromosome 1q41. Rat Ush2a has been localized by radiation hybrid mapping to rat chromosome 13 between d13rat49 and d13rat76. The mouse and rat genes, similar to human USH2A, are expressed primarily in retina and cochlea. Mouse Ush2a encodes a 161-kDa protein that shows 68% identity and 9% similarity to the human USH2A protein. Rat Ush2a encodes a 167-kDa protein with 64% identity and 10% similarity to the human protein and 81% identity and 5% similarity to the mouse USH2A protein. The predicted amino acid sequence of the mouse and rat proteins, like their human counterpart, contains a leader sequence, an amino-terminal globular domain, 10 laminin epidermal growth factor domains, and four carboxy-terminal fibronectin type III motifs. Within situ hybridization, we compared the cellular expression of the USH2A gene in rat, mouse, and human retinas. USH2A mRNA in the adult rat, mouse, and human is expressed in the cells of the outer nuclear layer of the retina, one of the target tissues of the disease. In the developing rat retina, Ush2a mRNA expression appears in the neuroepithelium at embryonic day 17.
AB - Usher syndrome type IIA (MIM: 27601) is an autosomal recessive disorder characterized by moderate to severe congenital deafness and progressive retinitis pigmentosa. We recently identified the human Usher syndrome type IIA gene (USH2A) on chromosome 1q41, which encodes a protein possessing 10 laminin epidermal growth factor and four fibronectin type 3 domains, both commonly observed in extracellular matrix proteins. To gain insight into the pathogenesis of Usher syndrome type IIA, we isolated and characterized the murine (Ush2a) and rat (ratUsh2a) orthologs of human USH2A. We mapped mouseUsh2a by fluorescence in situ hybridization to mouse chromosome 1 in the region syntenic to human chromosome 1q41. Rat Ush2a has been localized by radiation hybrid mapping to rat chromosome 13 between d13rat49 and d13rat76. The mouse and rat genes, similar to human USH2A, are expressed primarily in retina and cochlea. Mouse Ush2a encodes a 161-kDa protein that shows 68% identity and 9% similarity to the human USH2A protein. Rat Ush2a encodes a 167-kDa protein with 64% identity and 10% similarity to the human protein and 81% identity and 5% similarity to the mouse USH2A protein. The predicted amino acid sequence of the mouse and rat proteins, like their human counterpart, contains a leader sequence, an amino-terminal globular domain, 10 laminin epidermal growth factor domains, and four carboxy-terminal fibronectin type III motifs. Within situ hybridization, we compared the cellular expression of the USH2A gene in rat, mouse, and human retinas. USH2A mRNA in the adult rat, mouse, and human is expressed in the cells of the outer nuclear layer of the retina, one of the target tissues of the disease. In the developing rat retina, Ush2a mRNA expression appears in the neuroepithelium at embryonic day 17.
KW - Extracellular matrix protein
KW - Gene identification
KW - Usher syndrome
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U2 - 10.1006/geno.2002.6823
DO - 10.1006/geno.2002.6823
M3 - Article
C2 - 12160733
AN - SCOPUS:0036993149
SN - 0888-7543
VL - 80
SP - 195
EP - 203
JO - Genomics
JF - Genomics
IS - 2
ER -