Reproduction and maternal behavior in insulin-regulated aminopeptidase (IRAP) knockout mice

During human pregnancy, a circulating form of insulin-regulated aminopeptidase (IRAP EC 3.4.11.3), often termed oxytocinase or placental leucine aminopeptidase (PLAP), is present in plasma. It is proposed that circulating IRAP plays an important role in regulating the circulating levels of oxytocin...

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Published in:Peptides (New York, N.Y. : 1980) Vol. 30; no. 10; pp. 1861 - 1865
Main Authors: Pham, Vi, Burns, Peta, Albiston, Anthony L., Yeatman, Holly R., Ng, Leelee, Diwakarla, Shanti, Chai, Siew Yeen
Format: Journal Article
Language:English
Published: New York, NY Elsevier Inc 01.10.2009
Elsevier
Subjects:
Amino Acid Sequence
Animals
Biological and medical sciences
Cystinyl Aminopeptidase - genetics
Cystinyl Aminopeptidase - metabolism
Female
Fundamental and applied biological sciences. Psychology
Humans
IRAP
Male
Maternal Behavior - physiology
Mice
Mice, Knockout
Molecular Sequence Data
Oxytocin
Oxytocinase
Pregnancy
Reproduction - physiology
Vasopressin
Vertebrates: endocrinology
Pregnancy
Oxytocinase
IRAP
Oxytocin
Vasopressin
Parental behavior
Pancreatic hormone
Rodentia
Neuropeptide
Insulin
Maternal behavior
Vertebrata
Reproduction
Mammalia
Mouse
Animal
Neurohypophyseal hormone
Mutation
ISSN:0196-9781, 1873-5169, 1873-5169
Online Access:Get full text
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Summary:During human pregnancy, a circulating form of insulin-regulated aminopeptidase (IRAP EC 3.4.11.3), often termed oxytocinase or placental leucine aminopeptidase (PLAP), is present in plasma. It is proposed that circulating IRAP plays an important role in regulating the circulating levels of oxytocin and/or vasopressin during pregnancy. We assessed the reproductive and maternal profile of global IRAP knock out mice. No differences in the reproductive profile were observed, with normal gestational period, litter size and parturition recorded. However, western blot analysis of pregnant mouse serum, failed to detect IRAP, a result which was confirmed by fluorimetric IRAP enzyme assay. A review of the literature revealed that the presence of IRAP in the maternal circulation during pregnancy has been only reported in humans. Moreover, the sequence, Phe 154 Ala 155, identified as the cleavage site for the release of soluble IRAP, is restricted to members of the homindae family. Therefore the absence of IRAP from the circulation in mice, and other species during pregnancy, is due to the inability of a secretase to cleave placental IRAP to produce a soluble form of the enzyme. Given the expression of IRAP in areas of the brain associated with oxytocin modulated maternal behavior, we also investigated whether the IRAP global knockout mice had improved maternal responses. Using standard tests to assess maternal behavior, including pup retrieval, feeding and nurturing, no differences between knock out and wild type dams were observed. In conclusion, the physiological significance of circulating IRAP during human pregnancy cannot be addressed by investigations on mice.
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ISSN:0196-9781
1873-5169
1873-5169
DOI:10.1016/j.peptides.2009.07.019