Disease relevance of Amn

• We demonstrate that Cubn is not properly localized to the cell surface in Amn(-/-) tissues in the embryo and adult mouse, and that adult chimeras exhibit selective proteinuria of Cubn ligands [1].
• Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia [2].
• Variations of the Amnionless gene in recurrent spontaneous abortions [3].

High impact information on Amn

• The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation [2].
• Here we report that the gene Amn encodes a novel type I transmembrane protein that is expressed exclusively in the extra-embryonic visceral endoderm layer during gastrulation [4].
• To explore whether Amn participates in the development or function of KPT and intestinal epithelia and to gain insight into the function of Amn during gastrulation, we constructed Amn(-/-) ES cell<-->+/+ blastocyst chimeras [1].
• We show that Amn is also expressed in kidney proximal tubules (KPT) and intestinal epithelium, which, like the VE, are polarized epithelia specialized for resorption and secretion [1].
• Impaired primitive streak assembly in the mouse amnionless (amn) mutant results in the absence of non-axial trunk mesoderm, a derivative of the middle region of the primitive streak [1].

Biological context of Amn

• This gene maps to the site of transgene insertion; it is transcribed during gastrulation, and its expression is disrupted in amn mutant embryos [5].
• A gene encoding a 7.5-kb transcript has been identified at a junction between the integrated transgene and host chromosome 12 sequences that meets three criteria expected of a candidate amn gene [5].
• Interspecific backcross and fluorescence in situ hybridization analyses map the transgene insertion, and thus the amn mutation, to the distal region of mouse chromosome 12, which has synteny with human chromosome 14q32 [5].
• To gain insight into primitive streak assembly and function, we have conducted a detailed phenotypic characterization of amnionless, a transgene-induced insertional mouse mutation that arrests embryonic development during gastrulation [6].
• BACKGROUND: Cubilin is a peripheral membrane protein that interacts with the integral membrane proteins megalin and amnionless to mediate ligand endocytosis by absorptive epithelia such as the extraembryonic visceral endoderm (VE) [7].

Anatomical context of Amn

• We report the identification of a new recessive prenatal lethal insertional mutation, amnionless (amn). amn mutant embryos first appear abnormal during the Early Streak stage, between E6.5 and E7.0, when they initiate mesoderm production [5].
• In addition, the epiblast of amn mutants fails to increase significantly in size after E7.0, indicating that middle primitive streak assembly is mechanistically tied to the growth of the embryo during gastrulation [1].

References