Craniofacial abnormalities resulting from targeted disruption of the murine Sim2 gene

被引：46

作者：

Shamblott, MJ ^{[1
]}

Bugg, EM ^{[1
]}

Lawler, AM ^{[1
]}

Gearhart, JD ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21287 USA

来源：

DEVELOPMENTAL DYNAMICS | 2002年 / 224卷 / 04期

关键词：

mouse; cleft palate; aerophagia; hyaluronan synthase;

D O I：

10.1002/dvdy.10116

中图分类号：

R602 [外科病理学、解剖学]; R32 [人体形态学];

学科分类号：

100101 ;

摘要：

Sim2 is a member of the basic helix-loop-helix PAS transcription factor gene family and is evolutionarily related to the Drosophila single-minded gene, a key regulator of central nervous system midline development. In an effort to determine the biological roles of Sim2 in mammalian development, we disrupted the murine Sim2 gene through gene targeting. Mice homozygous for the disrupted allele (Sim2 -/-) exhibit a cleft of the secondary palate and malformations of the tongue and pterygoid processes of the sphenoid bone. These craniofacial malformations are the most probable cause of aerophagia (air swallowing with subsequent accumulation of air in the gastrointestinal tract) and postnatal death exhibited by Sim2 -/- mice. The developing palates of the Sim2 -/- mice are hypocellular, and at embryonic day 14.5 contain excess extracellular matrix component hyaluronan (HA) compared with heterozygotes and homozygous wild-type littermates. HA plays an important role in the regulation and mechanics of palate development. Its premature accumulation in Sim2 -/- animal palates suggests a regulatory role for Sim2 in HA synthesis and in the establishment of craniofacial architecture. (C) 2002 Wiley-Liss, Inc.

引用

页码：373 / 380

页数：8

共 29 条

[1]

BRADLEY A, 1992, CIBA F SYMP, V165, P256

[2]

BRINKLEY LL, 1986, J EMBRYOL EXP MORPH, V96, P111

[3]

Carson F. L., 1997, HISTOTECHNOLOGY SELF

[4] Cloning of two human homologs of the Drosophila single-minded gene SIM1 on chromosome 6q and SIM2 on 21q within the down syndrome chromosomal region [J].

Chrast, R ;

Scott, HS ;

Chen, HM ;

Kudoh, J ;

Rossier, C ;

Minoshima, S ;

Wang, YM ;

Shimizu, N ;

Antonarakis, SE .

GENOME RESEARCH, 1997, 7 (06) :615-624

[5]

Ema M, 1996, MOL CELL BIOL, V16, P5865

[6] Expression patterns of two murine homologs of Drosophila single-minded suggest possible roles in embryonic patterning and in the pathogenesis of down syndrome [J].

Fan, CM ;

Kuwana, E ;

Bulfone, A ;

Fletcher, CF ;

Copeland, NG ;

Jenkins, NA ;

Crews, S ;

Martinez, S ;

Puelles, L ;

Rubenstein, JLR ;

TessierLavigne, M .

MOLECULAR AND CELLULAR NEUROSCIENCE, 1996, 7 (01) :1-16

[7] A TECHNIQUE FOR RADIOLABELING DNA RESTRICTION ENDONUCLEASE FRAGMENTS TO HIGH SPECIFIC ACTIVITY [J].

FEINBERG, AP ;

VOGELSTEIN, B .

ANALYTICAL BIOCHEMISTRY, 1983, 132 (01) :6-13

[8]

FERGUSON M, 1987, J ANAT, V125, P555

[9]

FERGUSON MWJ, 1988, DEVELOPMENT, V103, P41

[10] TRANSCRIPTIONAL ACTIVATION DOMAINS OF THE SINGLE-MINDED BHLH PROTEIN ARE REQUIRED FOR CNS MIDLINE CELL-DEVELOPMENT [J].

FRANKS, RG ;

CREWS, ST .

MECHANISMS OF DEVELOPMENT, 1994, 45 (03) :269-277

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