Clarke L, Hepworth W B, Carey J C, Seegmiller R E
Department of Zoology, Brigham Young University, Provo, Utah 84602.
Teratology. 1988 Dec;38(6):565-70. doi: 10.1002/tera.1420380604.
Mice homozygous for either of two mutations, chondrodysplasia (cho) or cartilage matrix deficiency (cmd), have short-limbed chondrodystrophy. This phenotype includes retrognathia, relative macroglossia, and cleft palate. It has been postulated that the cleft palate in these mice is the result of tongue obstruction during palatogenesis. Agnathia associated with microglossia is an independent spontaneously occurring defect in the strains bearing these mutations. The coincidental occurrence of agnathia-microglossia with chondrodystrophy lends itself to the study of the mechanism of cleft palate formation. We examined approximate midsagittal histological sections of normal and chondrodystrophic newborn mice, both with and without agnathia. Mandibular measurements and examinations of palate closure and tongue structure were made from photographic prints. Typical chondrodystrophic mutants with cleft palates had a mean mandibular length that was 66% of normal and a tongue that appeared large relative to the shortened mandible. Chondrodystrophic mutants with agnathia and microglossia had a mean mandibular length that was further reduced to 30% of normal, yet had a closed palate. We also observed two nonagnathic chondrodystrophic mutants that had slightly decreased mandibular lengths, microglossia, and closed palates. These observations suggest that tongue obstruction during palatogenesis is the pathogenetic mechanism of cleft palate in chondrodystrophic mice. A similar tongue obstruction hypothesis has been proposed as the mechanism of cleft palate formation in the human Pierre Robin sequence, which consists of retrognathia, glossoptosis, and cleft palate. This mechanistic hypothesis has been challenged, but our findings support the tongue obstruction hypothesis in the Robin cleft.
纯合子携带软骨发育异常（cho）或软骨基质缺乏（cmd）这两种突变之一的小鼠，患有短肢性软骨发育不良。这种表型包括下颌后缩、相对巨舌症和腭裂。据推测，这些小鼠的腭裂是由于腭形成过程中舌头阻塞所致。与小舌症相关的无颌畸形是携带这些突变的品系中一种独立的自发出现的缺陷。无颌畸形 - 小舌症与软骨发育不良的同时出现有助于研究腭裂形成的机制。我们检查了正常和软骨发育不良的新生小鼠的近似矢状面组织学切片，包括有无无颌畸形的情况。通过照片打印对下颌进行测量，并检查腭闭合情况和舌头结构。典型的患有腭裂的软骨发育不良突变体的下颌平均长度为正常的66%，且相对于缩短的下颌，舌头显得较大。患有无颌畸形和小舌症的软骨发育不良突变体的下颌平均长度进一步降至正常的30%，但腭是闭合的。我们还观察到两个无无颌畸形的软骨发育不良突变体，它们的下颌长度略有减少，有小舌症，且腭是闭合的。这些观察结果表明，腭形成过程中的舌头阻塞是软骨发育不良小鼠腭裂的发病机制。类似的舌头阻塞假说已被提出作为人类皮埃尔·罗宾序列（由下颌后缩、舌后坠和腭裂组成）中腭裂形成的机制。这一机制假说受到了挑战，但我们的研究结果支持罗宾腭裂中的舌头阻塞假说。
