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Gene Review:

Hba-a2 - hemoglobin alpha, adult chain 2

Mus musculus

Synonyms: alpha 2 globin

Weiss, I.M. et al., Bernet, A. et al., Weiss, I.M. et al., Albitar, M. et al., Fabry, M.E. et al., et al.

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Disease relevance of Hba-a2

Using a transient transfection system, we demonstrate that in murine erythroleukemia cells the CS mRNA is unstable compared with the normal alpha 2-globin mRNA [1].

High impact information on Hba-a2

A line of transgenic mice with two cointegrated transgenes, the human beta S- and alpha 2-globin genes, linked to the beta-globin locus control region was produced and bred with mice carrying a deletion of the mouse beta major-globin gene [2].
In clones from which HS-40 had been deleted, human alpha-globin gene expression was severely reduced, although basal levels of alpha 1 and alpha 2-globin mRNA expression representing less than 3% of the level in control cell lines were detected [3].
To account for these results, we propose that the cis-acting elements form a complex or determinant in the normal alpha 2-globin mRNA which protects the message from degradation in erythroid cells [4].
Three cytidine-rich regions which are required for longevity of the alpha 2-globin mRNA were identified [4].
In contrast, both the CS and alpha 2-globin mRNAs are stable in several nonerythroid cell lines [1].

Biological context of Hba-a2

These results suggest that translational readthrough disrupts a determinant associated with the alpha 2-globin 3' NTR which is required for mRNA stability in erythroid cells [1].
Sequence analysis of the cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in an otherwise normal alpha 2-globin gene [5].
To define the cis-acting sequences which comprise this erythroid cell-specific stability determinant, scanning mutagenesis was performed on the alpha 2-globin 3' NTR, and the stability of each mutant mRNA was examined during transient expression [4].

Other interactions of Hba-a2

Analysis of human embryonic and early fetal erythroid RNA samples confirmed this possibility; levels of mRNA encoded by the two alpha-globin loci are equal in the embryo and subsequently shift to dominant expression of the alpha 2-globin locus at week 8 in utero [6].

References

Erythroid cell-specific determinants of alpha-globin mRNA stability. Weiss, I.M., Liebhaber, S.A. Mol. Cell. Biol. (1994) [Pubmed]
High expression of human beta S- and alpha-globins in transgenic mice: erythrocyte abnormalities, organ damage, and the effect of hypoxia. Fabry, M.E., Costantini, F., Pachnis, A., Suzuka, S.M., Bank, N., Aynedjian, H.S., Factor, S.M., Nagel, R.L. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
Targeted inactivation of the major positive regulatory element (HS-40) of the human alpha-globin gene locus. Bernet, A., Sabatier, S., Picketts, D.J., Ouazana, R., Morlé, F., Higgs, D.R., Godet, J. Blood (1995) [Pubmed]
Erythroid cell-specific mRNA stability elements in the alpha 2-globin 3' nontranslated region. Weiss, I.M., Liebhaber, S.A. Mol. Cell. Biol. (1995) [Pubmed]
Molecular basis for alpha-thalassemia associated with the structural mutant hemoglobin Suan-Dok (alpha 2 109leu----arg). Weiss, I., Cash, F.E., Coleman, M.B., Pressley, A., Adams, J.G., Sanguansermsri, T., Liebhaber, S.A., Steinberg, M.H. Blood (1990) [Pubmed]
Developmental switch in the relative expression of the alpha 1- and alpha 2-globin genes in humans and in transgenic mice. Albitar, M., Cash, F.E., Peschle, C., Liebhaber, S.A. Blood (1992) [Pubmed]

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HBA1	Bos taurus
HBA	Bos taurus
LOC100855558	Canis lupus familiaris
LOC100855540	Canis lupus familiaris
HBAA	Gallus gallus
LOC100858011	Gallus gallus
HBA2	Homo sapiens
HBA1	Homo sapiens
HBA2	Macaca mulatta
HBA2	Macaca mulatta
Hba-a1	Mus musculus
LOC287167	Rattus norvegicus
hba1	Xenopus (Silurana) tropicalis

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