DOI: 10.1073/pnas.2332851100. <i>In vivo</i> reduction of amyloid-β by a mutant copper transporter

In vivo reduction of amyloid-β by a mutant copper transporter

10.1073/pnas.2332851100

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-β (Aβ) peptide. To explore this relationship in vivo , toxic-milk ( tx J ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust Aβ deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive tx J mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma Aβ levels. In addition, homozygosity for tx J increased survival of young TgCRND8 mice and lowered endogenous CNS Aβ at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the tx J mutation on CNS Aβ burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of Aβ peptide.

Bibliography

Phinney, A. L., Drisaldi, B., Schmidt, S. D., Lugowski, S., Coronado, V., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., Chishti, M. A., Cox, D. W., Mathews, P. M., Nixon, R. A., Carlson, G. A., George-Hyslop, P. S., & Westaway, D. (2003). In vivo reduction of amyloid-Î² by a mutant copper transporter. Proceedings of the National Academy of Sciences, 100(24), 14193â14198.

Authors 17

Amie L. Phinney (first)
Bettina Drisaldi (additional)
Stephen D. Schmidt (additional)
Stan Lugowski (additional)
Veronica Coronado (additional)
Yan Liang (additional)
Patrick Horne (additional)
Jing Yang (additional)
Joannis Sekoulidis (additional)
Janaky Coomaraswamy (additional)
M. Azhar Chishti (additional)
Diane W. Cox (additional)
Paul M. Mathews (additional)
Ralph A. Nixon (additional)
George A. Carlson (additional)
Peter St George-Hyslop (additional)
David Westaway (additional)

References 56 Referenced 178

Braak, E., Griffing, K., Arai, K., Bohl, J., Bratzke, H. & Braak, H. (1999) Eur. Arch. Psychiatry Clin. Neurosci. 249, Suppl. 3, 14–22. / Eur. Arch. Psychiatry Clin. Neurosci. (1999)
10.1016/S0197-0186(02)00050-5
10.1385/JMN:17:2:137
10.1007/BF02796622
Atwood, C. S., Huang, X., Moir, R. D., Tanzi, R. E. & Bush, A. I. (1999) Met. Ions Biol. Syst. 36, 309–364.10093929 / Met. Ions Biol. Syst. (1999)
10.1016/S1367-5931(99)00073-3
Ehmann, W. D., Markesbery, W. R., Alauddin, M., Hossain, T. I. & Brubaker, E. H. (1986) Neurotoxicology 7, 195–206.3714121 / Neurotoxicology (1986)
10.1016/0022-510X(95)00018-W
Thompson, C. M., Markesbery, W. R., Ehmann, W. D., Mao, Y. X. & Vance, D. E. (1988) Neurotoxicology 9, 1–7.3393299 / Neurotoxicology (1988)
Cornett, C. R., Markesbery, W. R. & Ehmann, W. D. (1998) Neurotoxicology 19, 339–345.9621340 / Neurotoxicology (1998)
10.1126/science.271.5254.1406
10.1074/jbc.M300629200
10.1016/S0021-9258(19)85394-2
10.1074/jbc.273.21.12817
10.1046/j.1432-1327.2000.01767.x
10.1016/S0021-9258(18)47062-7
10.1074/jbc.272.42.26464
10.1046/j.1471-4159.2000.0751219.x
10.1074/jbc.274.33.23223
10.1042/bj3440461
10.1038/35050110
10.1074/jbc.M100710200
Cox D. W. & Roberts E. A. (1998) in Sleisenger and Fordtran's Gastrointestinal and Liver Disease eds. Feldman M. Schlarschmidt B. F. & Sleisenger M. H. (Saunders Philadelphia) pp. 1104–1111.
10.1074/jbc.272.34.21461
10.1093/hmg/9.13.1927
10.1006/bbrc.2001.4445
10.1016/0022-510X(87)90275-9
10.1016/0887-8994(88)90022-7
10.1093/hmg/5.10.1619
10.1093/hmg/10.4.361
10.1007/s00335-001-3021-y
Bronson, R. T., Sweet, H. O. & Davisson, M. T. (1995) Mouse Genome 93, 152–154. / Mouse Genome (1995)
10.1016/0092-8674(89)90608-9
10.1038/nm0197-67
10.1016/0267-6605(90)90001-C
10.1002/jbm.820251204
Lindquist, R. R. (1969) Arch. Pathol. 87, 370–379.5766764 / Arch. Pathol. (1969)
Mouton P. R. (2000) The Stereologer Handbook (Systems Planning and Analysis Alexandria VA).
Paxinos G. & Frankin K. B. J. (2001) The Mouse Brain in Stereotaxic Coordinates (Academic San Diego).
10.1016/S0197-4580(01)00267-6
10.1523/JNEUROSCI.18-05-01743.1998
10.1074/jbc.M205208200
10.1074/jbc.M204379200
10.1093/oxfordjournals.jhered.a109751
10.1016/S0021-9975(08)80268-X
Biempica, L., Rauch, H., Quintana, N. & Sternlieb, I. (1988) Lab. Invest. 59, 500–508.2845190 / Lab. Invest. (1988)
10.1016/0896-6273(95)90107-8
10.1016/S0197-4580(02)00120-3
10.1073/pnas.2332818100
10.1074/jbc.274.10.6483
10.1093/hmg/6.11.1951
10.1074/jbc.272.30.18939
10.1073/pnas.092034699
10.1073/pnas.151261398
10.1046/j.1471-4159.2002.00889.x
10.1016/S0896-6273(01)00317-8

Dates

Type	When
Created	21 years, 9 months ago (Nov. 25, 2003, 3:59 p.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 9:29 a.m.)
Indexed	4 weeks ago (July 30, 2025, 10:27 a.m.)
Issued	21 years, 9 months ago (Nov. 14, 2003)
Published	21 years, 9 months ago (Nov. 14, 2003)
Published Online	21 years, 9 months ago (Nov. 14, 2003)
Published Print	21 years, 9 months ago (Nov. 25, 2003)

Funders 0

None

BibTeX

@article{Phinney_2003, title={In vivo reduction of amyloid-β by a mutant copper transporter}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.2332851100}, DOI={10.1073/pnas.2332851100}, number={24}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Phinney, Amie L. and Drisaldi, Bettina and Schmidt, Stephen D. and Lugowski, Stan and Coronado, Veronica and Liang, Yan and Horne, Patrick and Yang, Jing and Sekoulidis, Joannis and Coomaraswamy, Janaky and Chishti, M. Azhar and Cox, Diane W. and Mathews, Paul M. and Nixon, Ralph A. and Carlson, George A. and George-Hyslop, Peter St and Westaway, David}, year={2003}, month=nov, pages={14193–14198} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        30
      ]
    ],
    "date-time": "2025-07-30T14:27:22Z",
    "timestamp": 1753885642034
  },
  "reference-count": 56,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "24",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2003,
        11,
        25
      ]
    ]
  },
  "abstract": "<jats:p>\n            Cu ions have been suggested to enhance the assembly and pathogenic potential of the Alzheimer's disease amyloid-\u03b2 (A\u03b2) peptide. To explore this relationship\n            <jats:italic>in vivo</jats:italic>\n            , toxic-milk (\n            <jats:italic>tx</jats:italic>\n            <jats:sup>J</jats:sup>\n            ) mice with a mutant ATPase7b transporter favoring elevated Cu levels were analyzed in combination with the transgenic (Tg) CRND8 amyloid precursor protein mice exhibiting robust A\u03b2 deposition. Unexpectedly, TgCRND8 mice homozygous for the recessive\n            <jats:italic>tx</jats:italic>\n            <jats:sup>J</jats:sup>\n            mutation examined at 6 months of age exhibited a reduced number of amyloid plaques and diminished plasma A\u03b2 levels. In addition, homozygosity for\n            <jats:italic>tx</jats:italic>\n            <jats:sup>J</jats:sup>\n            increased survival of young TgCRND8 mice and lowered endogenous CNS A\u03b2 at times before detectable increases in Cu in the CNS. These data suggest that the beneficial effect of the\n            <jats:italic>tx</jats:italic>\n            <jats:sup>J</jats:sup>\n            mutation on CNS A\u03b2 burden may proceed by a previously undescribed mechanism, likely involving increased clearance of peripheral pools of A\u03b2 peptide.\n          </jats:p>",
  "DOI": "10.1073/pnas.2332851100",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        11,
        25
      ]
    ],
    "date-time": "2003-11-25T20:59:06Z",
    "timestamp": 1069793946000
  },
  "page": "14193-14198",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 178,
  "title": "<i>In vivo</i>\n            reduction of amyloid-\u03b2 by a mutant copper transporter",
  "prefix": "10.1073",
  "volume": "100",
  "author": [
    {
      "given": "Amie L.",
      "family": "Phinney",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Bettina",
      "family": "Drisaldi",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Stephen D.",
      "family": "Schmidt",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Stan",
      "family": "Lugowski",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Veronica",
      "family": "Coronado",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Yan",
      "family": "Liang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Patrick",
      "family": "Horne",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Jing",
      "family": "Yang",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Joannis",
      "family": "Sekoulidis",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Janaky",
      "family": "Coomaraswamy",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "M. Azhar",
      "family": "Chishti",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Diane W.",
      "family": "Cox",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Paul M.",
      "family": "Mathews",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Ralph A.",
      "family": "Nixon",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "George A.",
      "family": "Carlson",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "Peter St",
      "family": "George-Hyslop",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    },
    {
      "given": "David",
      "family": "Westaway",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Center for Research in Neurodegenerative Diseases, Faculty of Dentistry, Department of Medicine, Division of Neurology, University Health Network, and Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada M5S 3H2; Nathan Kline Institute, Orangeburg, NY 10962; Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada T6G 2H7; and McLaughlin Research Institute, Great Falls, MT 59405"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2003,
        11,
        14
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_2_1_2",
      "first-page": "14",
      "volume": "249",
      "year": "1999",
      "unstructured": "Braak, E., Griffing, K., Arai, K., Bohl, J., Bratzke, H. & Braak, H. (1999) Eur. Arch. Psychiatry Clin. Neurosci. 249, Suppl. 3, 14\u201322.",
      "journal-title": "Eur. Arch. Psychiatry Clin. Neurosci."
    },
    {
      "key": "e_1_3_2_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0197-0186(02)00050-5"
    },
    {
      "key": "e_1_3_2_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1385/JMN:17:2:137"
    },
    {
      "key": "e_1_3_2_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF02796622"
    },
    {
      "key": "e_1_3_2_5_2",
      "first-page": "309",
      "volume": "36",
      "year": "1999",
      "unstructured": "Atwood, C. S., Huang, X., Moir, R. D., Tanzi, R. E. & Bush, A. I. (1999) Met. Ions Biol. Syst. 36, 309\u2013364.10093929",
      "journal-title": "Met. Ions Biol. Syst."
    },
    {
      "key": "e_1_3_2_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S1367-5931(99)00073-3"
    },
    {
      "key": "e_1_3_2_7_2",
      "first-page": "195",
      "volume": "7",
      "year": "1986",
      "unstructured": "Ehmann, W. D., Markesbery, W. R., Alauddin, M., Hossain, T. I. & Brubaker, E. H. (1986) Neurotoxicology 7, 195\u2013206.3714121",
      "journal-title": "Neurotoxicology"
    },
    {
      "key": "e_1_3_2_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-510X(95)00018-W"
    },
    {
      "key": "e_1_3_2_9_2",
      "first-page": "1",
      "volume": "9",
      "year": "1988",
      "unstructured": "Thompson, C. M., Markesbery, W. R., Ehmann, W. D., Mao, Y. X. & Vance, D. E. (1988) Neurotoxicology 9, 1\u20137.3393299",
      "journal-title": "Neurotoxicology"
    },
    {
      "key": "e_1_3_2_10_2",
      "first-page": "339",
      "volume": "19",
      "year": "1998",
      "unstructured": "Cornett, C. R., Markesbery, W. R. & Ehmann, W. D. (1998) Neurotoxicology 19, 339\u2013345.9621340",
      "journal-title": "Neurotoxicology"
    },
    {
      "key": "e_1_3_2_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.271.5254.1406"
    },
    {
      "key": "e_1_3_2_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M300629200"
    },
    {
      "key": "e_1_3_2_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)85394-2"
    },
    {
      "key": "e_1_3_2_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.273.21.12817"
    },
    {
      "key": "e_1_3_2_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1432-1327.2000.01767.x"
    },
    {
      "key": "e_1_3_2_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)47062-7"
    },
    {
      "key": "e_1_3_2_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.42.26464"
    },
    {
      "key": "e_1_3_2_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.2000.0751219.x"
    },
    {
      "key": "e_1_3_2_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.33.23223"
    },
    {
      "key": "e_1_3_2_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1042/bj3440461"
    },
    {
      "key": "e_1_3_2_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/35050110"
    },
    {
      "key": "e_1_3_2_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M100710200"
    },
    {
      "key": "e_1_3_2_23_2",
      "unstructured": "Cox D. W. & Roberts E. A. (1998) in Sleisenger and Fordtran's Gastrointestinal and Liver Disease eds. Feldman M. Schlarschmidt B. F. & Sleisenger M. H. (Saunders Philadelphia) pp. 1104\u20131111."
    },
    {
      "key": "e_1_3_2_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.34.21461"
    },
    {
      "key": "e_1_3_2_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/9.13.1927"
    },
    {
      "key": "e_1_3_2_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/bbrc.2001.4445"
    },
    {
      "key": "e_1_3_2_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-510X(87)90275-9"
    },
    {
      "key": "e_1_3_2_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0887-8994(88)90022-7"
    },
    {
      "key": "e_1_3_2_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/5.10.1619"
    },
    {
      "key": "e_1_3_2_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/10.4.361"
    },
    {
      "key": "e_1_3_2_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s00335-001-3021-y"
    },
    {
      "key": "e_1_3_2_32_2",
      "first-page": "152",
      "volume": "93",
      "year": "1995",
      "unstructured": "Bronson, R. T., Sweet, H. O. & Davisson, M. T. (1995) Mouse Genome 93, 152\u2013154.",
      "journal-title": "Mouse Genome"
    },
    {
      "key": "e_1_3_2_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(89)90608-9"
    },
    {
      "key": "e_1_3_2_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nm0197-67"
    },
    {
      "key": "e_1_3_2_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0267-6605(90)90001-C"
    },
    {
      "key": "e_1_3_2_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jbm.820251204"
    },
    {
      "key": "e_1_3_2_37_2",
      "first-page": "370",
      "volume": "87",
      "year": "1969",
      "unstructured": "Lindquist, R. R. (1969) Arch. Pathol. 87, 370\u2013379.5766764",
      "journal-title": "Arch. Pathol."
    },
    {
      "key": "e_1_3_2_38_2",
      "unstructured": "Mouton P. R. (2000) The Stereologer Handbook (Systems Planning and Analysis Alexandria VA)."
    },
    {
      "key": "e_1_3_2_39_2",
      "unstructured": "Paxinos G. & Frankin K. B. J. (2001) The Mouse Brain in Stereotaxic Coordinates (Academic San Diego)."
    },
    {
      "key": "e_1_3_2_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0197-4580(01)00267-6"
    },
    {
      "key": "e_1_3_2_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1523/JNEUROSCI.18-05-01743.1998"
    },
    {
      "key": "e_1_3_2_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M205208200"
    },
    {
      "key": "e_1_3_2_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.M204379200"
    },
    {
      "key": "e_1_3_2_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/oxfordjournals.jhered.a109751"
    },
    {
      "key": "e_1_3_2_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9975(08)80268-X"
    },
    {
      "key": "e_1_3_2_46_2",
      "first-page": "500",
      "volume": "59",
      "year": "1988",
      "unstructured": "Biempica, L., Rauch, H., Quintana, N. & Sternlieb, I. (1988) Lab. Invest. 59, 500\u2013508.2845190",
      "journal-title": "Lab. Invest."
    },
    {
      "key": "e_1_3_2_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0896-6273(95)90107-8"
    },
    {
      "key": "e_1_3_2_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0197-4580(02)00120-3"
    },
    {
      "key": "e_1_3_2_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.2332818100"
    },
    {
      "key": "e_1_3_2_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.274.10.6483"
    },
    {
      "key": "e_1_3_2_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/hmg/6.11.1951"
    },
    {
      "key": "e_1_3_2_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1074/jbc.272.30.18939"
    },
    {
      "key": "e_1_3_2_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.092034699"
    },
    {
      "key": "e_1_3_2_54_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.151261398"
    },
    {
      "key": "e_1_3_2_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1046/j.1471-4159.2002.00889.x"
    },
    {
      "key": "e_1_3_2_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0896-6273(01)00317-8"
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.2332851100",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        13
      ]
    ],
    "date-time": "2022-04-13T13:29:16Z",
    "timestamp": 1649856556000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.2332851100"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2003,
        11,
        14
      ]
    ]
  },
  "references-count": 56,
  "journal-issue": {
    "issue": "24",
    "published-print": {
      "date-parts": [
        [
          2003,
          11,
          25
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.2332851100"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.2332851100",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2003,
        11,
        14
      ]
    ]
  },
  "assertion": [
    {
      "value": "2003-05-12",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2003-11-14",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}