Developmental retardation, microcephaly, and peptiduria in mice without aminopeptidase P1
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- Developmental retardation, microcephaly, and peptiduria in mice without aminopeptidase P1
- Sang Ho Yoon; Young-Soo Bae; Mi-Sun Mun; Kyeong-Yeol Park; Sang-Kyu Ye; Eunjoon Kim; Myoung-Hwan Kim
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.429, no.3-4, pp.204 - 209
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Cytosolic aminopeptidase P1 (APP1) is one of the three known mammalian aminopeptidase Ps (APPs) that cleave the N-terminal amino acid residue of peptides in which the penultimate amino acid is proline. In mammals, many biologically active peptides have a highly conserved N-terminal penultimate proline. However, little is known about the physiological role of APP1. In addition, there is no direct evidence to associate a deficiency in APP1 with metabolic diseases. Although two human subjects with reduced APP activity exhibited peptiduria, it is unclear which of the three APP isoforms is responsible for this disorder. In this study, we generated APP1-deficient mice by knocking out Xpnpep1. Mouse APP1 deficiency causes severe growth retardation, microcephaly, and modest lethality. In addition, imino-oligopeptide excretion was observed in urine samples from APP1-deficient mice. These results suggest an essential role for APP1-mediated peptide metabolism in body and brain development, and indicate a strong causal link between APP1 deficiency and peptiduria. (C) 2012 Elsevier Inc. All rights reserved.
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