Linkage Relations of Flexed-Tail in Peromyscus

R. R. Huestis; Greta Lindstedt

doi:10.1086/281325

BMP4/Madh5 Dependent Signaling Is Required for the Expansion of a Population of Stress Erythroid Progenitors in the Fetal Liver.

Blood ◽

10.1182/blood.v106.11.4195.4195 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4195-4195

Author(s):

Robert F. Paulson ◽

Prashanth Porayette

Keyword(s):

Bone Marrow ◽

Steady State ◽

Fetal Liver ◽

Erythroid Progenitors ◽

Acute Anemia ◽

Erythroid Response ◽

Stress Erythropoiesis ◽

And Control ◽

Flexed Tail

Abstract Fetal liver hematopoiesis is primarily erythropoiesis, which robustly produces erythrocytes to meet the growing need of the developing embryo. In many ways fetal liver erythropoiesis resembles stress erythropoiesis in the adult, where in response to acute anemia, a unique population of stress erythroid progenitors is rapidly expanded in the spleen. The development of these stress progenitors requires BMP4/Madh5 dependent signals. Spleen stress progenitors exhibit properties that are distinct from bone marrow steady state progenitors in that they are able to rapidly form large BFU-E colonies, which require only Epo stimulation for their generation. Mice mutant at the flexed-tail locus exhibit a defective stress erythroid response because of a mutation in Madh5. In addition to this defect, flexed-tail mice also exhibit a severe fetal-neonatal anemia. We have analyzed fetal liver erythropoiesis in flexed-tail and control embryos. We show that BMP4 is expressed in the fetal liver and its expression correlates with the time of maximum erythropoiesis. In flexed-tail mutant embryos the expression is delayed and this correlates with both a delay and a defect in the expansion of erythroid progenitors. Our analysis also shows that the fetal liver contains two types of erythroid progenitors. One type exhibits the properties of stress BFU-E found in the adult spleen, which are compromised in flexed-tail embryos and a second type that is similar to bone marrow steady state BFU-E. These data demonstrate that BMP4 dependent signaling drives the expansion of erythroid progenitors in the fetal liver in a manner similar to stress erythropoiesis in the adult spleen.

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The Flexed-Tail-Anemia Gene (f) and Induced Leukemia in Mice

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/12.5.1119 ◽

1952 ◽

Keyword(s):

Flexed Tail

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Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: Analysis of mitomycin C-induced micronuclei

Mutation Research/Genetic Toxicology ◽

10.1016/0165-1218(96)00044-4 ◽

1996 ◽

Vol 370 (2) ◽

pp. 99-106

Author(s):

Cesare Urlando ◽

Flora Krasnoshtein ◽

John A. Meddle ◽

Manuel Buchwald

Keyword(s):

Mitomycin C ◽

Fanconi Anemia ◽

Flexed Tail

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An intronic sequence mutated in flexed-tail mice regulates splicing of Smad5

Mammalian Genome ◽

10.1007/s00335-007-9074-9 ◽

2007 ◽

Vol 18 (12) ◽

pp. 852-860 ◽

Cited By ~ 15

Author(s):

Shailaja Hegde ◽

Laurie E. Lenox ◽

Andrew Lariviere ◽

Prashanth Porayette ◽

John M. Perry ◽

...

Keyword(s):

Intronic Sequence ◽

Flexed Tail

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BMP4 and Madh5 regulate the erythroid response to acute anemia

Blood ◽

10.1182/blood-2004-02-0703 ◽

2005 ◽

Vol 105 (7) ◽

pp. 2741-2748 ◽

Cited By ~ 120

Author(s):

Laurie E. Lenox ◽

John M. Perry ◽

Robert F. Paulson

Keyword(s):

Steady State ◽

Mutant Mice ◽

Systemic Response ◽

Erythroid Progenitors ◽

New Model ◽

Acute Anemia ◽

Erythroid Response ◽

Flexed Tail

Abstract Acute anemia initiates a systemic response that results in the rapid mobilization and differentiation of erythroid progenitors in the adult spleen. The flexed-tail (f) mutant mice exhibit normal steady-state erythropoiesis but are unable to rapidly respond to acute erythropoietic stress. Here, we show that f/f mutant mice have a mutation in Madh5. Our analysis shows that BMP4/Madh5-dependent signaling, regulated by hypoxia, initiates the differentiation and expansion of erythroid progenitors in the spleen. These findings suggest a new model where stress erythroid progenitors, resident in the spleen, are poised to respond to changes in the microenvironment induced by acute anemia.

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