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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Veröffentlicht in:	Peptides (New York, N.Y. : 1980) Jg. 30; H. 10; S. 1861 - 1865
Hauptverfasser:	Pham, Vi, Burns, Peta, Albiston, Anthony L., Yeatman, Holly R., Ng, Leelee, Diwakarla, Shanti, Chai, Siew Yeen
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York, NY Elsevier Inc 01.10.2009 Elsevier
Schlagworte:	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
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Abstract	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.
AbstractList	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. 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 super(154) Ala super(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. 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, Phe154 Ala155, 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.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, Phe154 Ala155, 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. 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, Phe154 Ala155, 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.
Author	Burns, Peta Chai, Siew Yeen Diwakarla, Shanti Pham, Vi Albiston, Anthony L. Ng, Leelee Yeatman, Holly R.
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CitedBy_id	crossref_primary_10_1016_j_bbr_2019_112150 crossref_primary_10_1016_j_ygcen_2017_06_002 crossref_primary_10_3389_fcell_2020_585237 crossref_primary_10_1186_s12902_018_0234_6 crossref_primary_10_1016_j_yhbeh_2011_12_014 crossref_primary_10_1111_jne_12141 crossref_primary_10_1038_s41598_023_31540_9 crossref_primary_10_1093_aob_mcq265 crossref_primary_10_1111_jne_12186 crossref_primary_10_1016_j_lfs_2015_04_023 crossref_primary_10_1038_s41467_020_16471_7 crossref_primary_10_1016_j_peptides_2025_171352 crossref_primary_10_1016_j_peptides_2024_171150 crossref_primary_10_1016_j_ultrasmedbio_2013_09_026 crossref_primary_10_1111_j_1476_5381_2011_01402_x crossref_primary_10_1093_humupd_dmw021
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Keywords	Pregnancy Oxytocinase IRAP Oxytocin Vasopressin Parental behavior Pancreatic hormone Rodentia Neuropeptide Insulin Maternal behavior Vertebrata Reproduction Mammalia Mouse Animal Neurohypophyseal hormone Mutation
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Snippet	During human pregnancy, a circulating form of insulin-regulated aminopeptidase (IRAP EC 3.4.11.3), often termed oxytocinase or placental leucine aminopeptidase...
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SubjectTerms	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
Title	Reproduction and maternal behavior in insulin-regulated aminopeptidase (IRAP) knockout mice
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