Article

Microcytosis in ank/ank mice and the role of ANKH in promoting erythroid differentiation.

Genetics and Development Division, Toronto Western Research Institute, Toronto, Ontario, Canada.
Experimental Cell Research (impact factor: 3.58). 01/2008; 313(20):4120-9. DOI:10.1016/j.yexcr.2007.09.008
Source: PubMed

ABSTRACT Progressive ankylosis (Ank and the human homolog, ANKH) is a transmembrane protein which regulates transport of inorganic pyrophosphate (PPi). ank/ank mice with a mutated ank gene, have calcification and bone ankylosis of the affected joints. In the course of studying these mutant mice, we found that they have microcytosis. These mutant mice have lower mean red blood cell volume (MCV) and lower hemoglobin content in red cells (mean corpuscular hemoglobin, MCH) than normal mice. Using quantitative real-time PCR analysis, we showed that Ank was expressed in the E/Meg bipotent precursor, BFU-E, CFU-E, but there was no Ank expression in the hemoglobinizing erythroblasts. Stable ANKH transfectants in K562 cells highly expressed two immature erythroid cell markers, E-cadherin and endoglin. Enhanced Erythropoietin (Epo) expression and downregulation of SHP-1 were detected in these transfectants. Consequently, the autocrine Epo-EpoR signaling pathway was activated, as evidenced by higher p-Tyr JAK2, p-Tyr EpoR and p-Tyr STAT5B in the ANKH transfectants. Our results revealed a novel function of ANKH in the promotion of early erythroid differentiation in K562 cells. We also showed that ank/ank mice have lower serum levels of Epo than the normal littermates, and this is the likely cause of microcytosis in these mutant mice.

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Keywords

ank/ank mice
 
ANKH
 
ANKH transfectants
 
autocrine Epo-EpoR signaling pathway
 
bone ankylosis
 
E/Meg bipotent precursor
 
hemoglobinizing erythroblasts
 
higher p-Tyr JAK2
 
immature erythroid cell markers
 
mutant mice
 
mutated ank gene
 
normal mice
 
novel function
 
p-Tyr EpoR
 
p-Tyr STAT5B
 
Progressive ankylosis
 
quantitative real-time PCR analysis
 
red blood cell volume
 
regulates transport
 
Stable ANKH transfectants