Gong S G
Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, 1011 North University Avenue, Ann Arbor, MI 48109-1078, USA.
Cleft Palate Craniofac J. 2001 Sep;38(5):486-91. doi: 10.1597/1545-1569_2001_038_0486_pamaoa_2.0.co_2.
Since its first description, the A strain of mice have been utilized extensively as models to study the processes involved in clefting of the midfacial region. Of the A substrains, the A/WySn has a spontaneous rate of clefting of the lip of about 20% to 30%. The A/WySn mouse model was utilized in this study to analyze and compare the phenotypic and molecular changes in the midfacial region of embryos with and without cleft.
Scanning electron microscopy and skeletal and cartilage preparations of newborn A/WySn pups showed the presence of bilateral and unilateral clefts of the lips and the disruption of the skeletal and cartilaginous components of the mice with clefts of the lip. The expression of the msx1 homeobox gene was analyzed by whole mount in situ hybridization of A/WySn embryos at different stages of midfacial development. The results showed that there was misregulation of the expression of the msx1 gene in embryos with cleft, with a persistence of expression in the distal growing tips of the midfacial processes and in areas that have fused in normal embryos without cleft.
Although the genetic defect in A/WySn mice is not known, a possible candidate gene has been mapped to a corresponding human chromosome carrying retinoic acid receptor alpha, and there exists a possibility that msx1 is in the same genetic pathway affected by the mutation of the gene in A/WySn.
自首次被描述以来，A品系小鼠已被广泛用作模型，以研究面中部区域腭裂形成过程中涉及的各种过程。在A亚品系中，A/WySn品系小鼠唇裂的自发发生率约为20%至30%。本研究使用A/WySn小鼠模型，分析和比较有唇裂和无唇裂胚胎面中部区域的表型和分子变化。
新生A/WySn幼崽的扫描电子显微镜检查以及骨骼和软骨标本显示，存在双侧和单侧唇裂，且唇裂小鼠的骨骼和软骨成分遭到破坏。通过对不同面中部发育阶段的A/WySn胚胎进行全胚胎原位杂交，分析了msx1同源框基因的表达情况。结果显示，唇裂胚胎中msx1基因的表达失调，在面中部突起的远端生长尖端以及正常无唇裂胚胎中已融合的区域持续表达。
尽管尚不清楚A/WySn小鼠的基因缺陷，但已将一个可能的候选基因定位到携带视黄酸受体α的相应人类染色体上，并且存在msx1处于受A/WySn基因突变影响的相同遗传途径中的可能性。
