Mapping of genetic modifiers of Eya1(bor/bor) in CAST/EiJ and BALB/cJ that suppress cochlear aplasia and associated deafness

作者：Niu Haoru; Li Xin; Makmura Linna; Friedman Rick A^*

来源：Mammalian Genome, 2008, 19(9): 634-639.

DOI：10.1007/s00335-008-9145-6

Mice homozygous for the hypomorphic allele Eya1(bor) exhibit cochlear aplasia, with associated deafness, and renal hypoplasia, similar to Branchio-Oto-Renal syndrome (BOR) in humans. Although much is known about the genetics of the disease, little is known about the factors that modify its phenotypic expression. We have recently detailed two modifier loci (Mead1 and Mead2) in a C3HeB/FeJ-Eva1(bor/+) x C57BL/6 J intercross that suppress the ear-related phenotypes in our hypomorphic mutants. In this study we report corroborating evidence for our initial finding with the identification of two modifier loci mapping to the same region in CAST/EiJ and BALB/cJ. Furthermore, we describe an additional locus (Mea3) on chromosome 19 in CAST/EiJ, within which the previously cloned suppressor Nxf1 resides. The suppression effect on cochlear coiling was studied on congenic line(s) for each protective allele. The penetrance and suppressor strength of these alleles vary by strain and locus. Eya1(bor/bor) hypomorphs, when homozygous for each of the three protective alleles (CAST/EiJ, C57BL/6 J, or BALB/cJ) at the Mead1 or Mead2 locus, exhibit completely penetrant suppression of cochlear agenesis. At the Mend1 locus, the C57BL/6 J and BALB/cJ alleles have comparable strengths. At the Mead2 locus, the C57BL/6 J and CAST/EiJ alleles have comparable strengths. In contrast, mice with genotype Eya1(bor/bor)Mead3(CAST/CAST) exhibit incomplete penetrance (50%) and a wide range of cochlear coiling (1/4-11/2 turns). The identification of these additional modifier alleles could provide crucial clues for evaluating the candidate genes.

• 出版日期2008-9
• 单位华中科技大学