Tanner Stephan M, Aminoff Maria, Wright Fred A, Liyanarachchi Sandya, Kuronen Mervi, Saarinen Anne, Massika Orit, Mandel Hanna, Broch Harald, de la Chapelle Albert
Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Nat Genet. 2003 Mar;33(3):426-9. doi: 10.1038/ng1098. Epub 2003 Feb 18.
The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the tenth day of gestation but seem to lack the mesodermal layers that normally produce the trunk. The Amn protein has one transmembrane domain separating a larger, N-terminal extracellular region and a smaller, C-terminal cytoplasmic region. The extracellular region harbors a cysteine-rich domain resembling those occurring in Chordin, found in Xenopus laevis embryos, and Sog, found in Drosophila melanogaster. As these cysteine-rich domains bind bone morphogenetic proteins (Bmps), it has been speculated that the cysteine-rich domain in Amn also binds Bmps. We show that homozygous mutations affecting exons 1-4 of human AMN lead to selective malabsorption of vitamin B12 (a phenotype associated with megaloblastic anemia 1, MGA1; OMIM 261100; refs. 5,6) in otherwise normal individuals, suggesting that the 5' end of AMN is dispensable for embryonic development but necessary for absorption of vitamin B12. When the 5' end of AMN is truncated by mutations, translation is initiated from alternative downstream start codons.
位于小鼠12号染色体上的无羊膜基因（Amn）编码一种I型跨膜蛋白，该蛋白在原肠胚形成期间于胚外脏层表达。通过转基因插入产生的amn突变纯合子小鼠没有羊膜。这些胚胎严重受损，可存活至妊娠第10天，但似乎缺少正常情况下产生躯干的中胚层。Amn蛋白有一个跨膜结构域，将较大的N端细胞外区域和较小的C端细胞质区域分隔开。细胞外区域含有一个富含半胱氨酸的结构域，类似于非洲爪蟾胚胎中发现的脊索蛋白（Chordin）和黑腹果蝇中发现的短胚轴蛋白（Sog）中的结构域。由于这些富含半胱氨酸的结构域能结合骨形态发生蛋白（Bmp），因此推测Amn中富含半胱氨酸的结构域也能结合Bmp。我们发现，影响人类AMN外显子1至4的纯合突变会导致原本正常的个体出现维生素B12的选择性吸收不良（一种与巨幼细胞贫血1相关的表型，MGA1；OMIM 261100；参考文献5,6），这表明AMN的5'端对胚胎发育并非必需，但对维生素B12的吸收是必需的。当AMN的5'端因突变而被截断时，翻译会从下游的替代起始密码子开始。
