title: Establishment of a recessive mutant small-eye rat with lens involution and retinal detachment associated with partial deletion and rearrangement of the Cryba1 gene.
abstract: From our stock of SDRs (Sprague-Dawley rats), we established a mutant strain having small opaque eyes and named it HiSER (Hirosaki small-eye rat). The HiSER phenotype is progressive and autosomal recessive. In HiSER eyes, disruption and involution of the lens, thickening of the inner nuclear layer, detachment and aggregation of the retina, rudimentary muscle in the ciliary body and cell infiltration in the vitreous humour were observed. Genetic linkage analysis using crossing with Brown Norway rat suggested that the causative gene(s) is located on chromosome 10. Microarray analysis showed that the expression level of the Cryba1 gene encoding βA3/A1-crystallin on chromosome 10 was markedly decreased in HiSER eyes. Genomic PCR revealed deletion of a 3.6-kb DNA region encompassing exons 4-6 of the gene in HiSERs. In HiSER eyes, a chimaeric transcript of the gene containing exons 1-3 and an approximately 250-bp sequence originating from the 3'-UTR of the Nufip2 gene, located downstream of the breakpoint in the opposite direction, was present. Whereas the chimaeric transcript was expressed in HiSER eyes, neither normal nor chimaeric βA3/A1-crystallin proteins were detected by Western blot analysis. Real-time RT (reverse transcription)-PCR analysis revealed that expression level of the Nufip2 gene in the HiSER eye was 40% of that in the SDR eye. These results suggest that the disappearance of the βA3/A1-crystallin protein and, in addition, down-regulation of the Nufip2 gene as a consequence of gene rearrangement causes the HiSER phenotype.
authors: Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors: Toshiyuki
authors: T
authors: Yamada
authors: Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan Department of Biomedical Science, Hirosaki University Graduate School of Health Science, Hirosaki 036-8564, Japan.
authors: Naoki
authors: N
authors: Nanashima
authors: Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors: Takeshi
authors: T
authors: Shimizu
authors: Department of Molecular Function and Physiology, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan.
authors: Yosuke
authors: Y
authors: Nakazawa
authors: Department of Ophthalmology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors: Mitsuru
authors: M
authors: Nakazawa
authors: Department of Biochemistry and Genome Biology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan tsuchida@hirosaki-u.ac.jp).
authors: Shigeki
authors: S
authors: Tsuchida
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D003459:Crystallins / Q000235:genetics / Q000378:metabolism; D015321:Gene Rearrangement; D005808:Genes, Recessive; D007908:Lens, Crystalline / Q000002:abnormalities / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012163:Retinal Detachment / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017384:Sequence Deletion
chemical_list: D020413:3' Untranslated Regions; D003459:Crystallins; D016601:RNA-Binding Proteins; C526189:betaA3-crystallin, rat
keywords: Cryba1 gene; Nufip2 gene; lens involution; microphthalmia; retinal detachment; βA3/A1-crystallin