A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse
A mutation in the F-box gene, Fbxo11, causes otitis media in the Jeff mouse
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DOI：
10.1093/hmg/ddl403
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发表时间：
2006-11-15
影响因子：
3.5
通讯作者：
Brown, Steve D. M.
中科院分区：
文献类型：
--
作者：
Hardisty-Hughes, Rachel E.;Tateossian, Hilda;Brown, Steve D. M.
中耳炎（OM）是中耳的炎症，是儿童听力障碍和手术的最常见原因。已知复发性和慢性形式的OM具有很强的遗传成分，但对人类群体中涉及的潜在基因一无所知。我们先前已经鉴定了一种新的半显性小鼠突变体Jeff，其中杂合子发展为慢性化脓性OM（Hardisty，R.E.，Erven，A.，洛根，K.，莫尔斯，Guionaud，S.，Sancho-Oliver，S.，亨特，AJ，南达科他州布朗和Steel，K. P.（2003）耳聋小鼠突变体Jeff（Jf）是中耳炎的单基因模型。耳鼻喉科研究联合杂志，4，130-138.）并代表了人类慢性OM的模型。我们在这里证明，杰夫携带突变的F盒基因，Fbxo 11。Fbxo 11在胚胎晚期至出生后第13天的中耳上皮细胞中表达。与Jeff杂合子相比，Jeff纯合子表现出腭裂、面裂和围产期致死性。我们还分离和表征了一个额外的亚型突变等位基因，Mutt。杂种杂合子不发展OM，但杂种纯合子也显示面部裂开和腭裂异常。FBXO 11是最早被鉴定的分子之一，有助于OM的遗传病因学。此外，Fbxo 11的突变等位基因的隐性效应将该基因确定为人群中腭裂研究的重要候选基因。
Otitis media (OM), inflammation of the middle ear, is the most common cause of hearing impairment and surgery in children. Recurrent and chronic forms of OM are known to have a strong genetic component, but nothing is known of the underlying genes involved in the human population. We have previously identified a novel semi-dominant mouse mutant, Jeff, in which the heterozygotes develop chronic suppurative OM (Hardisty, R.E., Erven, A., Logan, K., Morse, S., Guionaud, S., Sancho-Oliver, S., Hunter, A.J., Brown, S.D. and Steel, K.P. (2003) The deaf mouse mutant Jeff (Jf) is a single gene model of otitis media. J. Assoc. Res. Otolaryngol., 4, 130-138.) and represent a model for chronic forms of OM in humans. We demonstrate here that Jeff carries a mutation in an F-box gene, Fbxo11. Fbxo11 is expressed in epithelial cells of the middle ears from late embryonic stages through to day 13 of postnatal life. In contrast to Jeff heterozygotes, Jeff homozygotes show cleft palate, facial clefting and perinatal lethality. We have also isolated and characterized an additional hypomorphic mutant allele, Mutt. Mutt heterozygotes do not develop OM but Mutt homozygotes also show facial clefting and cleft palate abnormalities. FBXO11 is one of the first molecules to be identified, contributing to the genetic aetiology of OM. In addition, the recessive effects of mutant alleles of Fbxo11 identify the gene as an important candidate for cleft palate studies in the human population.