A novel spontaneous mutation of BCAR3 results in extrusion cataracts in CF#1 mouse strain

Abstract

A substrain of mice originating from the CF#1 strain (an outbred colony) reared at Osaka Prefecture University (CF#1/lr mice) develops cataracts beginning at 4 weeks of age. Affected mice were fully viable and fertile and developed cataracts by 14 weeks of age. Histologically, CF#1/lr mice showed vacuolation of the lens cortex, swollen lens fibers, lens rupture and nuclear extrusion. To elucidate the mode of inheritance, we analyzed heterozygous mutant hybrids generated from CF#1/lr mice and wild-type BALB/c mice. None of the heterozygous mutants were affected, and the ratio of affected to unaffected mice was 1:3 among the offspring of the heterozygous mutants. For the initial genome-wide screening and further mapping, we used affected progeny of CF#1/lr × (CF#1/lr × BALB/c) mice. We concluded that the cataracts in CF#1/lr mice are inherited through an autosomal recessive mutation and that the mutant gene is located on mouse chromosome 3 between D3Mit79 and D3Mit216. In this region, we identified 8 genes associated with ocular disease. All 8 genes were sequenced and a novel point mutation (1 bp insertion of cytosine) in exon 7 of the Bcar3 gene was identified. This mutation produced a premature stop codon and a truncated protein. In conclusion, we have identified the first spontaneous mutation in the Bcar3 gene associated with lens extrusion cataracts. This novel cataract model may provide further knowledge of the molecular biology of cataractogenesis and the function of the BCAR3 protein.

Prediction and prognostic significance of BCAR3 expression in patients with multiple myeloma

“…Studies have shown that the BCAR3 gene is the first spontaneous mutation associated with cataracts caused by lens compression. This new cataract model could provide further knowledge about the function of BCAR3 protein [21]. In the study of tamoxifen in the treatment of metastatic breast cancer, high expression of BCAR3 is related to good progression-free survival, and the expression level of BCAR3 in primary breast tumors is relatively low, which is related to the survival rate of distant metastasis [14].…”

Integrative transcriptomic profiling of ncRNAs and mRNAs in developing mouse lens

“…Previous studies have validated the function of Vax2os, which is involved in neurotransmitter transport during mouse retinal development and plays an important role in regulating eye development ( Alfano et al, 2005 ; Chen et al, 2021 ). LncRNAs TCONS_00094093 were cis-targeted with BCAR3 adaptor protein ( BCAR3 ), the signaling mediated by which is required for the maintenance of the structural integrity of the ocular lens ( Near et al, 2009 ; Kondo et al, 2016 ). LncRNAs Prox1os were cis-targeted with Prospero Homeobox 1 ( PROX1 ) and trans-target with crystallin beta A1 ( CRYBA1 ) and BFSP2 , which has been showed is crucial for mouse lens fiber differentiation and elongation ( Wigle et al, 1999 ; Song et al, 2009 ; Audette et al, 2016 ; Joseph et al, 2023 ).…”

Table6.XLSX

“…Previous studies have validated the function of Vax2os, which is involved in neurotransmitter transport during mouse retinal development and plays an important role in regulating eye development (Alfano et al, 2005;Chen et al, 2021). LncRNAs TCONS_00094093 were cis-targeted with BCAR3 adaptor protein (BCAR3), the signaling mediated by which is required for the maintenance of the structural integrity of the ocular lens (Near et al, 2009;Kondo et al, 2016). LncRNAs Prox1os were cis-targeted with Prospero Homeobox 1 (PROX1) and trans-target with crystallin beta A1 (CRYBA1) and BFSP2, which has been showed is crucial for mouse lens fiber differentiation and elongation (Wigle et al, 1999;Song et al, 2009;Audette et al, 2016;Joseph et al, 2023).…”