Mice Haploinsufficient for Ets1 and Fli1 Display Middle Ear Abnormalities and Model Aspects of Jacobsen Syndrome

被引：12

作者：

Carpinelli, Marina R. ^{[1
,2
]}

Kruse, Elizabeth A. ^{[3
,5
]}

Arhatari, Benedicta D. ^{[6
]}

Debrincat, Marlyse A. ^{[5
]}

Ogier, Jacqueline M. ^{[1
,2
]}

Bories, Jean-Christophe ^{[7
]}

Kile, Benjamin T. ^{[5
]}

Burt, Rachel A. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia

[2] Univ Melbourne, HEARing Cooperat Res Ctr, Melbourne, Vic, Australia

[3] Univ Melbourne, Dept Med Biol, Melbourne, Vic, Australia

[4] Univ Melbourne, Dept Genet, Melbourne, Vic, Australia

[5] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia

[6] La Trobe Univ, Dept Phys, ARC Ctr Excellence Coherent Xray Sci, Bundoora, Vic 3083, Australia

[7] Inst Univ Hematol, INSERM, UMR 1126, Paris, France

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2015年 / 185卷 / 07期

基金：

英国医学研究理事会;

关键词：

PARIS-TROUSSEAU-SYNDROME; TRANSCRIPTION FACTOR; TECTORIAL MEMBRANE; DELETION; GENE; HEARING; CELLS; DEFICIENCY; MUTATIONS; DEAFNESS;

D O I：

10.1016/j.ajpath.2015.03.026

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

E26 transformation-specific 1 (ETS1) and friend leukemia integration 1 (FLI1) are members of the ETS family of transcription factors, of which there are 28 in humans. Both genes are hemizygous in Jacobsen syndrome, an 11q contiguous gene deletion disorder involving thrombocytopenia, facial dysmorphism, growth and mental retardation, malformation of the heart and other organs, and hearing impairment associated with recurrent ear infections. To determine whether any of these defects are because of hemizygosity for ETS1 and FLI1, we characterized the phenotype of mice heterozygous for mutant alleles of Ets1 and Fli1. Fli1(+/-) mice displayed mild thrombocytopenia, as did Ets1(+/-)Fli1(+/-) animals. Fli1(+/-) and Ets1(+/-)Fli1(+/-) mice also displayed craniofacial abnormalities, including a small middle ear cavity, short nasal bone, and malformed interface between the nasal bone process and cartilaginous nasal septum. They exhibited hearing impairment, otitis media, fusions of ossicles to the middle ear wall, and deformed stapes. Hearing impairment was more penetrant and stapes malformations were more severe in Ets1(+/-)Fli1(+/-) mice than in Fli1(+/-) mice, indicating partial functional redundancy of these transcription factors during auditory development. Our findings indicate that the short nose, otitis media, and hearing impairment in Jacobsen syndrome are Likely because of hemizygosity for ETS1 and FLI1.

引用

页码：1867 / 1876

页数：10

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