Mapping of genetic modifiers of Eya1 ( bor/bor ) in CAST/EiJ and BALB/cJ that suppress cochlear aplasia and associated deafness.
Mapping of genetic modifiers of Eya1 ( bor/bor ) in CAST/EiJ and BALB/cJ that suppress cochlear aplasia and associated deafness.
复制标题
CAST/EiJ 和 BALB/cJ 中抑制耳蜗发育不全和相关耳聋的 Eya1 ( bor/bor ) 基因修饰因子的定位。
DOI：
10.1007/s00335-008-9145-6
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Friedman,RickA
中科院分区：
文献类型：
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作者：
Niu,Haoru;Li,Xin;Makmura,Linna;Friedman,RickA
Mice homozygous for the hypomorphic alleleEya1borexhibit 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 (Mead1andMead2) in a C3HeB/FeJ-Eya1bor/+× 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 (Mead3) on chromosome 19 in CAST/EiJ, within which the previously cloned suppressorNxf1resides. 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.Eya1bor/borhypomorphs, when homozygous for each of the three protective alleles (CAST/EiJ, C57BL/6 J, or BALB/cJ) at theMead1orMead2locus, exhibit completely penetrant suppression of cochlear agenesis. At theMead1locus, the C57BL/6 J and BALB/cJ alleles have comparable strengths. At theMead2locus, the C57BL/6 J and CAST/EiJ alleles have comparable strengths. In contrast, mice with genotypeEya1bor/borMead3CAST/CASTexhibit incomplete penetrance (50%) and a wide range of cochlear coiling (1/4–1½ turns). The identification of these additional modifier alleles could provide crucial clues for evaluating the candidate genes.
