Gene structure and chromosomal localization of mouse Opa1 : its exclusion from the Bst locus

Comparison of mouse and human OPA1 sequences revealed 88% and 97% identity at the nucleotide and amino acid levels, respectively. Presence of alternatively spliced mRNAs as seen in human was conserved in the mouse. Screening of the whole mRNA coding sequence and of the 31 exons of Opa1 did not reveal any mutation in Bst. Using a radiation hybrid panel (T31), we mapped Opa1 to chromosome 16 between genetic markers D16Mit3 and D16Mit124, which is 10 cM centromeric to the Bst locus.On the basis of these results we conclude that Opa1 and Bst are distinct genes and that the Bst mouse is not the mouse model for DOA.Autosomal dominant optic atrophy (DOA), Kjer type [1], is the most common form of hereditary optic neuropathies with an estimated prevalence of 1:50 000 in most populations [2] and prevalence as high as 1:10 000 in Denmark [3]. The disease appears with an insidious onset of variable visual loss, optic nerve pallor, caecocentral visual field scotoma, and color vision deficit. Histopathological [4,5] and electrophysiological [6,7] studies suggest that the underlying defect is a retinal ganglion cell degeneration. Most families of DOA have been shown to map to 3q28-29 (OPA1, MIM 165500) [8-14]. The gene named OPA1 was subsequently identified [15,16] with more than 70 mutations described today [17-21]. One single family was found to determine a second locus (OPA4, MIM 605293) at 18q12.2-q12.3 [22]. OPA1 codes a mitochondrial dynamin-related GTPase that may play a role in the maintenance of mitochondrial morphology and DNA. Tissue specific expression of OPA1 alternatively spliced exons may underlie some specific neuronal requirements in OPA1 [18].In 1977, Southard et al. [23] identified a dominant mutation, belly spot and tail (Bst), which arose spontaneously in the C57BLKS mouse strain with in utero death of homozygotes. Heterozygous mice have a kinky tail, white feet and white spots at the ventral midline. In addition, approximately 50% of the Bst/+ mice, show a r