Mice Haploinsufficient for Ets1 and Fli1 display middle ear abnormalities and model aspects of Jacobsen syndrome

Marina R. Carpinelli, Elizabeth A. Kruse, Benedicta D. Arhatari, Marlyse A. Debrincat, Jacqueline M. Ogier, Jean-Christophe Bories, Benjamin T. Kile, Rachel A. Burt

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Article number2047
Pages (from-to)1867-1876
Number of pages10
JournalAmerican Journal of Pathology
Volume185
Issue number7
DOIs
Publication statusPublished - Jul 2015
Externally publishedYes

Cite this

Carpinelli, Marina R. ; Kruse, Elizabeth A. ; Arhatari, Benedicta D. ; Debrincat, Marlyse A. ; Ogier, Jacqueline M. ; Bories, Jean-Christophe ; Kile, Benjamin T. ; Burt, Rachel A. / Mice Haploinsufficient for Ets1 and Fli1 display middle ear abnormalities and model aspects of Jacobsen syndrome. In: American Journal of Pathology. 2015 ; Vol. 185, No. 7. pp. 1867-1876.
@article{d8f8f241dfa341b9bb63cb7a68f7723c,
title = "Mice Haploinsufficient for Ets1 and Fli1 display middle ear abnormalities and model aspects of Jacobsen syndrome",
abstract = "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.",
author = "Carpinelli, {Marina R.} and Kruse, {Elizabeth A.} and Arhatari, {Benedicta D.} and Debrincat, {Marlyse A.} and Ogier, {Jacqueline M.} and Jean-Christophe Bories and Kile, {Benjamin T.} and Burt, {Rachel A.}",
year = "2015",
month = "7",
doi = "10.1016/j.ajpath.2015.03.026",
language = "English",
volume = "185",
pages = "1867--1876",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "American Society for Investigative Pathology",
number = "7",

}

Mice Haploinsufficient for Ets1 and Fli1 display middle ear abnormalities and model aspects of Jacobsen syndrome. / Carpinelli, Marina R.; Kruse, Elizabeth A.; Arhatari, Benedicta D.; Debrincat, Marlyse A.; Ogier, Jacqueline M.; Bories, Jean-Christophe; Kile, Benjamin T.; Burt, Rachel A.

In: American Journal of Pathology, Vol. 185, No. 7, 2047, 07.2015, p. 1867-1876.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mice Haploinsufficient for Ets1 and Fli1 display middle ear abnormalities and model aspects of Jacobsen syndrome

AU - Carpinelli, Marina R.

AU - Kruse, Elizabeth A.

AU - Arhatari, Benedicta D.

AU - Debrincat, Marlyse A.

AU - Ogier, Jacqueline M.

AU - Bories, Jean-Christophe

AU - Kile, Benjamin T.

AU - Burt, Rachel A.

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84931352337&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2015.03.026

DO - 10.1016/j.ajpath.2015.03.026

M3 - Article

VL - 185

SP - 1867

EP - 1876

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 7

M1 - 2047

ER -