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Zinc finger protein, Hzf, is required for megakaryocyte development and hemostasis.

Kimura Y, Hart A, Hirashima M, Wang C, Holmyard D, Pittman J, Pang XL, Jackson CW, Bernstein A - J. Exp. Med. (2002)

Bottom Line: Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo.Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced alpha-granule substances in both megakaryocytes and platelets.These results indicate that Hzf plays important roles in regulating the synthesis of alpha-granule substances and/or their packing into alpha-granules during the process of megakaryopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.

ABSTRACT
Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C(2)H(2)-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced alpha-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of alpha-granule substances and/or their packing into alpha-granules during the process of megakaryopoiesis.

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The presence of megakaryocytes and normal aspects of megakaryocyte maturation in Hzf −/− mice. (A and B) Transverse sections through the spleens from Hzf +/+ (A) and Hzf −/− (B) mice, demonstrating the presence of megakaryocytes in each. A and B, original magnification: ×100. (C and D) Microscopic examination of bone marrow smears from Hzf +/+ (C) and Hzf −/− (D) mice, showing the presence of megakaryocytes in each. C and D, original magnification: ×100. (E) Flow cytometric analysis confirms no significant difference of megakaryocyte frequency between control and Hzf −/− mice. The proportion of megakaryocytes to bone marrow cells was performed after staining with 4A5 mAb, to murine megakaryocytes. Six mice, which were age- and sex-matched, were analyzed in each genotype with FACScan™. Results are presented as the means ±SD. (F) Representative megakaryocyte DNA ploidy in Hzf −/− mice. The proportion of cells in each ploidy class was determined by PI-staining after gated on 4A5-positive cells with FACScan™, demonstrating no effect of Hzf deficiency on endomitosis. Six mice, which were age- and sex-matched, were analyzed in each genotype. This data was representative with comparable results.
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fig4: The presence of megakaryocytes and normal aspects of megakaryocyte maturation in Hzf −/− mice. (A and B) Transverse sections through the spleens from Hzf +/+ (A) and Hzf −/− (B) mice, demonstrating the presence of megakaryocytes in each. A and B, original magnification: ×100. (C and D) Microscopic examination of bone marrow smears from Hzf +/+ (C) and Hzf −/− (D) mice, showing the presence of megakaryocytes in each. C and D, original magnification: ×100. (E) Flow cytometric analysis confirms no significant difference of megakaryocyte frequency between control and Hzf −/− mice. The proportion of megakaryocytes to bone marrow cells was performed after staining with 4A5 mAb, to murine megakaryocytes. Six mice, which were age- and sex-matched, were analyzed in each genotype with FACScan™. Results are presented as the means ±SD. (F) Representative megakaryocyte DNA ploidy in Hzf −/− mice. The proportion of cells in each ploidy class was determined by PI-staining after gated on 4A5-positive cells with FACScan™, demonstrating no effect of Hzf deficiency on endomitosis. Six mice, which were age- and sex-matched, were analyzed in each genotype. This data was representative with comparable results.

Mentions: To explore in greater detail the nature of the platelet defects described above, we characterized megakaryocytes from Hzf −/− mutant mice. No differences in the numbers of megakaryocytes were observed in the spleens and bone marrows of Hzf mutant mice, as determined morphologically and by flow cytometric analysis (Fig. 4 A–E).


Zinc finger protein, Hzf, is required for megakaryocyte development and hemostasis.

Kimura Y, Hart A, Hirashima M, Wang C, Holmyard D, Pittman J, Pang XL, Jackson CW, Bernstein A - J. Exp. Med. (2002)

The presence of megakaryocytes and normal aspects of megakaryocyte maturation in Hzf −/− mice. (A and B) Transverse sections through the spleens from Hzf +/+ (A) and Hzf −/− (B) mice, demonstrating the presence of megakaryocytes in each. A and B, original magnification: ×100. (C and D) Microscopic examination of bone marrow smears from Hzf +/+ (C) and Hzf −/− (D) mice, showing the presence of megakaryocytes in each. C and D, original magnification: ×100. (E) Flow cytometric analysis confirms no significant difference of megakaryocyte frequency between control and Hzf −/− mice. The proportion of megakaryocytes to bone marrow cells was performed after staining with 4A5 mAb, to murine megakaryocytes. Six mice, which were age- and sex-matched, were analyzed in each genotype with FACScan™. Results are presented as the means ±SD. (F) Representative megakaryocyte DNA ploidy in Hzf −/− mice. The proportion of cells in each ploidy class was determined by PI-staining after gated on 4A5-positive cells with FACScan™, demonstrating no effect of Hzf deficiency on endomitosis. Six mice, which were age- and sex-matched, were analyzed in each genotype. This data was representative with comparable results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193728&req=5

fig4: The presence of megakaryocytes and normal aspects of megakaryocyte maturation in Hzf −/− mice. (A and B) Transverse sections through the spleens from Hzf +/+ (A) and Hzf −/− (B) mice, demonstrating the presence of megakaryocytes in each. A and B, original magnification: ×100. (C and D) Microscopic examination of bone marrow smears from Hzf +/+ (C) and Hzf −/− (D) mice, showing the presence of megakaryocytes in each. C and D, original magnification: ×100. (E) Flow cytometric analysis confirms no significant difference of megakaryocyte frequency between control and Hzf −/− mice. The proportion of megakaryocytes to bone marrow cells was performed after staining with 4A5 mAb, to murine megakaryocytes. Six mice, which were age- and sex-matched, were analyzed in each genotype with FACScan™. Results are presented as the means ±SD. (F) Representative megakaryocyte DNA ploidy in Hzf −/− mice. The proportion of cells in each ploidy class was determined by PI-staining after gated on 4A5-positive cells with FACScan™, demonstrating no effect of Hzf deficiency on endomitosis. Six mice, which were age- and sex-matched, were analyzed in each genotype. This data was representative with comparable results.
Mentions: To explore in greater detail the nature of the platelet defects described above, we characterized megakaryocytes from Hzf −/− mutant mice. No differences in the numbers of megakaryocytes were observed in the spleens and bone marrows of Hzf mutant mice, as determined morphologically and by flow cytometric analysis (Fig. 4 A–E).

Bottom Line: Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo.Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced alpha-granule substances in both megakaryocytes and platelets.These results indicate that Hzf plays important roles in regulating the synthesis of alpha-granule substances and/or their packing into alpha-granules during the process of megakaryopoiesis.

View Article: PubMed Central - PubMed

Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada.

ABSTRACT
Using an expression gene trapping strategy, we recently identified a novel gene, hematopoietic zinc finger (Hzf), which encodes a protein containing three C(2)H(2)-type zinc fingers that is predominantly expressed in megakaryocytes. Here, we have examined the in vivo function of Hzf by gene targeting and demonstrated that Hzf is essential for megakaryopoiesis and hemostasis in vivo. Hzf-deficient mice exhibited a pronounced tendency to rebleed and had reduced alpha-granule substances in both megakaryocytes and platelets. These mice also had large, faintly stained platelets, whereas the numbers of both megakaryocytes and platelets were normal. These results indicate that Hzf plays important roles in regulating the synthesis of alpha-granule substances and/or their packing into alpha-granules during the process of megakaryopoiesis.

Show MeSH