Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour

Eishin Nakamura, Kenji Kadomatsu, Shigeki Yuasa, Hisako Muramatsu, Takayoshi Mamiya, Toshitaka Nabeshima, Qi Wen Fan, Kazuhiro Ishiguro, Tadahiko Igakura, Shuichiro Matsubara, Tadashi Kaname, Mitsuru Horiba, Hidehiko Saito, Takashi Muramatsu

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Background: Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. Results: Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(-/-) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(-/-) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(-/-) mice. Furthermore, 4 weeks after birth, Mdk(-/-) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. Conclusion: Midkine plays an important role in the regulation of postnatal development of the hippocampus.

Original languageEnglish
Pages (from-to)811-822
Number of pages12
JournalGenes to Cells
Volume3
Issue number12
DOIs
Publication statusPublished - 01-12-1998
Externally publishedYes

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Calcium-Binding Proteins
Hippocampus
Genes
Calbindin 2
Parturition
midkine
Dentate Gyrus
Short-Term Memory
Knockout Mice
Intercellular Signaling Peptides and Proteins
Anxiety
Brain

All Science Journal Classification (ASJC) codes

  • Genetics
  • Cell Biology

Cite this

Nakamura, Eishin ; Kadomatsu, Kenji ; Yuasa, Shigeki ; Muramatsu, Hisako ; Mamiya, Takayoshi ; Nabeshima, Toshitaka ; Fan, Qi Wen ; Ishiguro, Kazuhiro ; Igakura, Tadahiko ; Matsubara, Shuichiro ; Kaname, Tadashi ; Horiba, Mitsuru ; Saito, Hidehiko ; Muramatsu, Takashi. / Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour. In: Genes to Cells. 1998 ; Vol. 3, No. 12. pp. 811-822.
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title = "Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour",
abstract = "Background: Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. Results: Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(-/-) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(-/-) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(-/-) mice. Furthermore, 4 weeks after birth, Mdk(-/-) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. Conclusion: Midkine plays an important role in the regulation of postnatal development of the hippocampus.",
author = "Eishin Nakamura and Kenji Kadomatsu and Shigeki Yuasa and Hisako Muramatsu and Takayoshi Mamiya and Toshitaka Nabeshima and Fan, {Qi Wen} and Kazuhiro Ishiguro and Tadahiko Igakura and Shuichiro Matsubara and Tadashi Kaname and Mitsuru Horiba and Hidehiko Saito and Takashi Muramatsu",
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Nakamura, E, Kadomatsu, K, Yuasa, S, Muramatsu, H, Mamiya, T, Nabeshima, T, Fan, QW, Ishiguro, K, Igakura, T, Matsubara, S, Kaname, T, Horiba, M, Saito, H & Muramatsu, T 1998, 'Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour', Genes to Cells, vol. 3, no. 12, pp. 811-822. https://doi.org/10.1046/j.1365-2443.1998.00231.x

Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour. / Nakamura, Eishin; Kadomatsu, Kenji; Yuasa, Shigeki; Muramatsu, Hisako; Mamiya, Takayoshi; Nabeshima, Toshitaka; Fan, Qi Wen; Ishiguro, Kazuhiro; Igakura, Tadahiko; Matsubara, Shuichiro; Kaname, Tadashi; Horiba, Mitsuru; Saito, Hidehiko; Muramatsu, Takashi.

In: Genes to Cells, Vol. 3, No. 12, 01.12.1998, p. 811-822.

Research output: Contribution to journalArticle

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T1 - Disruption of the midkine gene (Mdk) resulted in altered expression of a calcium binding protein in the hippocampus of infant mice and their abnormal behaviour

AU - Nakamura, Eishin

AU - Kadomatsu, Kenji

AU - Yuasa, Shigeki

AU - Muramatsu, Hisako

AU - Mamiya, Takayoshi

AU - Nabeshima, Toshitaka

AU - Fan, Qi Wen

AU - Ishiguro, Kazuhiro

AU - Igakura, Tadahiko

AU - Matsubara, Shuichiro

AU - Kaname, Tadashi

AU - Horiba, Mitsuru

AU - Saito, Hidehiko

AU - Muramatsu, Takashi

PY - 1998/12/1

Y1 - 1998/12/1

N2 - Background: Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. However, its in vivo function has not been clarified. Results: Knockout mice lacking the MK gene (Mdk) showed no gross abnormalities. We closely analysed postnatal brain development in Mdk(-/-) mice using calcium binding proteins as markers to distinguish neuronal subpopulations. Intense and prolonged calretinin expression was found in the dentate gyrus granule cell layer of the hippocampus of infant Mdk(-/-) mice. In infant Mdk(+/+) mice, calretinin expression in the granule cell layer was weaker, and had disappeared by 4 weeks after birth, when calretinin expression still persisted in Mdk(-/-) mice. Furthermore, 4 weeks after birth, Mdk(-/-) mice showed a deficit in their working memory, as revealed by a Y-maze test, and had an increased anxiety, as demonstrated by the elevated plus-maze test. Conclusion: Midkine plays an important role in the regulation of postnatal development of the hippocampus.

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