The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1

Rebecca A. Wingert, Alison Brownlie, Jenna L. Galloway, Kimberly Dooley, Paula Fraenkel, Jennifer L. Axe, Alan J. Davidson, Bruce Barut, Laura Noriega, Xiaoming Sheng, Yi Zhou, F. van Bebber, E. Busch-Nentwich, R. Dahm, H. G. Frohnhöfer, H. Geiger, D. Gilmour, S. Holley, J. Hooge, D. Jülich & 29 others H. Knaut, F. Maderspacher, C. Neumann, Teresa Nicolson, C. Nüsslein-Volhard, H. Roehl, U. Schönberger, C. Seiler, M. Söllner, M. Sonawane, A. Wehner, C. Weiler, B. Schimdt, U. Hagner, E. Hennen, C. Kaps, A. Kirchner, T. I. Koblizek, U. Langheinrich, C. Metzger, R. Nordin, M. Pezzuti, K. Schlombs, J. deSantana-Stamm, T. Trowe, G. Vacun, A. Walker, C. Weiler, Leonard I. Zon

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests a hypochromic, microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1-like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b function using antisense morpholinos: revealed that this paralog was dispensable for hemoglobin production in red cells. tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2, and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cell.

Original languageEnglish (US)
Pages (from-to)6225-6235
Number of pages11
JournalDevelopment
Volume131
Issue number24
DOIs
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Transferrin Receptors
Zebrafish
Hemoglobins
Iron
Morpholinos
Erythroid Cells
Genetic Models
Cytochromes
Heme
Necrosis
Embryonic Structures
Central Nervous System
Erythrocytes
Metals
Brain
Growth
Genes

Keywords

  • Gene duplication
  • Hematopoiesis
  • Iron
  • Transferrin receptor
  • Zebrafish

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Wingert, R. A., Brownlie, A., Galloway, J. L., Dooley, K., Fraenkel, P., Axe, J. L., ... Zon, L. I. (2004). The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1. Development, 131(24), 6225-6235. https://doi.org/10.1242/dev.01540

The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1. / Wingert, Rebecca A.; Brownlie, Alison; Galloway, Jenna L.; Dooley, Kimberly; Fraenkel, Paula; Axe, Jennifer L.; Davidson, Alan J.; Barut, Bruce; Noriega, Laura; Sheng, Xiaoming; Zhou, Yi; van Bebber, F.; Busch-Nentwich, E.; Dahm, R.; Frohnhöfer, H. G.; Geiger, H.; Gilmour, D.; Holley, S.; Hooge, J.; Jülich, D.; Knaut, H.; Maderspacher, F.; Neumann, C.; Nicolson, Teresa; Nüsslein-Volhard, C.; Roehl, H.; Schönberger, U.; Seiler, C.; Söllner, M.; Sonawane, M.; Wehner, A.; Weiler, C.; Schimdt, B.; Hagner, U.; Hennen, E.; Kaps, C.; Kirchner, A.; Koblizek, T. I.; Langheinrich, U.; Metzger, C.; Nordin, R.; Pezzuti, M.; Schlombs, K.; deSantana-Stamm, J.; Trowe, T.; Vacun, G.; Walker, A.; Weiler, C.; Zon, Leonard I.

In: Development, Vol. 131, No. 24, 12.2004, p. 6225-6235.

Research output: Contribution to journalArticle

Wingert, RA, Brownlie, A, Galloway, JL, Dooley, K, Fraenkel, P, Axe, JL, Davidson, AJ, Barut, B, Noriega, L, Sheng, X, Zhou, Y, van Bebber, F, Busch-Nentwich, E, Dahm, R, Frohnhöfer, HG, Geiger, H, Gilmour, D, Holley, S, Hooge, J, Jülich, D, Knaut, H, Maderspacher, F, Neumann, C, Nicolson, T, Nüsslein-Volhard, C, Roehl, H, Schönberger, U, Seiler, C, Söllner, M, Sonawane, M, Wehner, A, Weiler, C, Schimdt, B, Hagner, U, Hennen, E, Kaps, C, Kirchner, A, Koblizek, TI, Langheinrich, U, Metzger, C, Nordin, R, Pezzuti, M, Schlombs, K, deSantana-Stamm, J, Trowe, T, Vacun, G, Walker, A, Weiler, C & Zon, LI 2004, 'The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1', Development, vol. 131, no. 24, pp. 6225-6235. https://doi.org/10.1242/dev.01540
Wingert RA, Brownlie A, Galloway JL, Dooley K, Fraenkel P, Axe JL et al. The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1. Development. 2004 Dec;131(24):6225-6235. https://doi.org/10.1242/dev.01540
Wingert, Rebecca A. ; Brownlie, Alison ; Galloway, Jenna L. ; Dooley, Kimberly ; Fraenkel, Paula ; Axe, Jennifer L. ; Davidson, Alan J. ; Barut, Bruce ; Noriega, Laura ; Sheng, Xiaoming ; Zhou, Yi ; van Bebber, F. ; Busch-Nentwich, E. ; Dahm, R. ; Frohnhöfer, H. G. ; Geiger, H. ; Gilmour, D. ; Holley, S. ; Hooge, J. ; Jülich, D. ; Knaut, H. ; Maderspacher, F. ; Neumann, C. ; Nicolson, Teresa ; Nüsslein-Volhard, C. ; Roehl, H. ; Schönberger, U. ; Seiler, C. ; Söllner, M. ; Sonawane, M. ; Wehner, A. ; Weiler, C. ; Schimdt, B. ; Hagner, U. ; Hennen, E. ; Kaps, C. ; Kirchner, A. ; Koblizek, T. I. ; Langheinrich, U. ; Metzger, C. ; Nordin, R. ; Pezzuti, M. ; Schlombs, K. ; deSantana-Stamm, J. ; Trowe, T. ; Vacun, G. ; Walker, A. ; Weiler, C. ; Zon, Leonard I. / The chianti zebrafish mutant provides a model for erythroid-specific disruption of transferrin receptor 1. In: Development. 2004 ; Vol. 131, No. 24. pp. 6225-6235.
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abstract = "Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. The zebrafish chianti (cia) mutant manifests a hypochromic, microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. We show that cia encodes tfr1a, which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. In the process of isolating zebrafish tfr1, we discovered two tfr1-like genes (tfr1a and tfr1b) and a single tfr2 ortholog. Abrogation of tfr1b function using antisense morpholinos: revealed that this paralog was dispensable for hemoglobin production in red cells. tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. Overexpression of mouse Tfr1, mouse Tfr2, and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cell.",
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AU - Brownlie, Alison

AU - Galloway, Jenna L.

AU - Dooley, Kimberly

AU - Fraenkel, Paula

AU - Axe, Jennifer L.

AU - Davidson, Alan J.

AU - Barut, Bruce

AU - Noriega, Laura

AU - Sheng, Xiaoming

AU - Zhou, Yi

AU - van Bebber, F.

AU - Busch-Nentwich, E.

AU - Dahm, R.

AU - Frohnhöfer, H. G.

AU - Geiger, H.

AU - Gilmour, D.

AU - Holley, S.

AU - Hooge, J.

AU - Jülich, D.

AU - Knaut, H.

AU - Maderspacher, F.

AU - Neumann, C.

AU - Nicolson, Teresa

AU - Nüsslein-Volhard, C.

AU - Roehl, H.

AU - Schönberger, U.

AU - Seiler, C.

AU - Söllner, M.

AU - Sonawane, M.

AU - Wehner, A.

AU - Weiler, C.

AU - Schimdt, B.

AU - Hagner, U.

AU - Hennen, E.

AU - Kaps, C.

AU - Kirchner, A.

AU - Koblizek, T. I.

AU - Langheinrich, U.

AU - Metzger, C.

AU - Nordin, R.

AU - Pezzuti, M.

AU - Schlombs, K.

AU - deSantana-Stamm, J.

AU - Trowe, T.

AU - Vacun, G.

AU - Walker, A.

AU - Weiler, C.

AU - Zon, Leonard I.

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KW - Gene duplication

KW - Hematopoiesis

KW - Iron

KW - Transferrin receptor

KW - Zebrafish

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