Genomes and Genes
Gene Symbol: Hbb-b2
Description: hemoglobin, beta adult minor chain
Alias: AI036344, Hbb2, Hbbt2, beta2, hemoglobin subunit beta-2, beta min, beta minor globin
- Hu X, Eszterhas S, Pallazzi N, Bouhassira E, Fields J, Tanabe O, et al. Transcriptional interference among the murine beta-like globin genes. Blood. 2007;109:2210-6 pubmed
- Kautz L, Jung G, Valore E, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46:678-84 pubmed publisher..ERFE expression is greatly increased in Hbb(th3/+) mice with thalassemia intermedia, where it contributes to the suppression of hepcidin and the systemic iron overload characteristic of this disease. ..
- Barrow J, Masannat J, BUNGERT J. Neutralizing the function of a ?-globin-associated cis-regulatory DNA element using an artificial zinc finger DNA-binding domain. Proc Natl Acad Sci U S A. 2012;109:17948-53 pubmed publisher..These results demonstrate that artificial DNA-binding proteins lacking effector domains are useful tools for studying and modulating the function of cis-regulatory DNA elements. ..
- SMITH E, Luc S, Croney D, Woodworth M, Greig L, Fujiwara Y, et al. Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood. 2016;128:2338-2342 pubmed publisher..These preclinical findings provide strong in vivo support for genetic modification of the enhancer for therapy of hemoglobin disorders. ..
- Basu P, Morris P, Haar J, Wani M, Lingrel J, Gaensler K, et al. KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo. Blood. 2005;106:2566-71 pubmed..KLF2 also plays a role in the maturation and/or stability of erythroid cells in the yolk sac. KLF2-/- embryos have a significantly increased number of primitive erythroid cells undergoing apoptotic cell death. ..
- Sankaran V, Xu J, Ragoczy T, Ippolito G, Walkley C, Maika S, et al. Developmental and species-divergent globin switching are driven by BCL11A. Nature. 2009;460:1093-7 pubmed publisher..By comparing the ontogeny of beta-globin gene regulation in mice and humans, we have shown that alterations in the expression of a trans-acting factor constitute a critical driver of gene expression changes during evolution. ..
- Romero J, Suzuka S, Nagel R, Fabry M. Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. Blood. 2004;103:2384-90 pubmed..We conclude that human globins are able to stimulate the activity and/or regulation of K-Cl cotransport in mouse red cells. These observations support the contention that HbS and HbC stimulate K-Cl cotransport in human red cells. ..
- Vadolas J, Wardan H, Bosmans M, Zaibak F, Jamsai D, Voullaire L, et al. Transgene copy number-dependent rescue of murine beta-globin knockout mice carrying a 183 kb human beta-globin BAC genomic fragment. Biochim Biophys Acta. 2005;1728:150-62 pubmed
- Blackburn A, Hill L, Roberts A, Wang J, Aud D, Jung J, et al. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk. Am J Pathol. 2007;170:2030-41 pubmed..The results identify a novel mammary tumor susceptibility locus in mice and support a role for DMBT1 in suppression of mammary tumors in both mice and women. ..
- Liu L, Zeng M, Stamler J. Hemoglobin induction in mouse macrophages. Proc Natl Acad Sci U S A. 1999;96:6643-7 pubmed..These data suggest alternative functions for globins in mammalian cells, and they challenge the prevailing view that the expression of alpha- and beta-globin genes is always balanced and coordinated. ..
- Konkel D, Maizel J, Leder P. The evolution and sequence comparison of two recently diverged mouse chromosomal beta--globin genes. Cell. 1979;18:865-73 pubmed..Change in such regions apparently occurs less by point mutation than by insertion, deletion and duplication of relatively short segments of the genome. ..
- Feng Y, Yang Y, Ortega M, Copeland J, Zhang M, Jacob J, et al. Early mammalian erythropoiesis requires the Dot1L methyltransferase. Blood. 2010;116:4483-91 pubmed publisher..1 transcription, thus controlling numbers of circulating erythroid and myeloid cells. ..
- Elorza A, Hyde B, Mikkola H, Collins S, Shirihai O. UCP2 modulates cell proliferation through the MAPK/ERK pathway during erythropoiesis and has no effect on heme biosynthesis. J Biol Chem. 2008;283:30461-70 pubmed publisher..Together, these results indicate that UCP2 is a regulator of erythropoiesis and suggests that inhibition of UCP2 function may contribute to the development of anemia. ..
- Chen W, Gu P, Jiang X, Ruan H, Li C, Gao X. Protein phosphatase 2A catalytic subunit ? (PP2Ac?) maintains survival of committed erythroid cells in fetal liver erythropoiesis through the STAT5 pathway. Am J Pathol. 2011;178:2333-43 pubmed publisher..Collectively, these data provide direct loss-of-function evidence demonstrating the importance of PP2Ac? for the survival of committed erythroid cells during fetal liver erythropoiesis...
- Yu Q, Stamenkovic I. Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion. Genes Dev. 1999;13:35-48 pubmed..Our observations indicate that CD44 serves to anchor MMP-9 on the cell surface and define a mechanism for CD44-mediated tumor invasion. ..
- Embury S, Mohandas N, Paszty C, Cooper P, Cheung A. In vivo blood flow abnormalities in the transgenic knockout sickle cell mouse. J Clin Invest. 1999;103:915-20 pubmed
- Liu X, Li X, Wang Y, Shu R, Wang L, Lu S, et al. Disruption of palladin leads to defects in definitive erythropoiesis by interfering with erythroblastic island formation in mouse fetal liver. Blood. 2007;110:870-6 pubmed..These data demonstrate that palladin is crucial for definitive erythropoiesis and erythroblastic island formation and, especially, required for normal function of macrophages in fetal liver. ..
- Yang B, Kirby S, Lewis J, Detloff P, Maeda N, Smithies O. A mouse model for beta 0-thalassemia. Proc Natl Acad Sci U S A. 1995;92:11608-12 pubmed..The heterozygous animals will be useful for studying the pathophysiology of thalassemias and have the potential of generating a model of sickle cell anemia when mated with appropriate transgenic animals. ..
- Römer I, Jungblut P, Reik W, Otto A, Klose J. A novel strategy to identify maternal and paternal inheritance in the mouse. Electrophoresis. 1995;16:823-30 pubmed..For the beta-group hemoglobins our results suggested parental effects on the transcriptional level. ..
- Bultman S, Gebuhr T, Magnuson T. A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev. 2005;19:2849-61 pubmed..Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling. ..
- Anderson E, Taylor M, Xue X, Ramakrishnan S, Martin A, Xie L, et al. Intestinal HIF2α promotes tissue-iron accumulation in disorders of iron overload with anemia. Proc Natl Acad Sci U S A. 2013;110:E4922-30 pubmed publisher..These data demonstrate that dysregulation of intestinal hypoxia and HIF2α signaling is critical for progressive iron overload in β-thalassemia and may be a novel therapeutic target in several anemic iron-overload disorders. ..
- Porcu S, Poddie D, Melis M, Cao A, Ristaldi M. beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice. Gene. 2005;351:11-7 pubmed..The results obtained support a general role of EKLF in beta-globin gene activation and are in agreement with models involving an advantage of the LCR proximal respect to distal gene. ..
- Siwaponanan P, Siegers J, Ghazali R, NG T, McColl B, Ng G, et al. Reduced PU.1 expression underlies aberrant neutrophil maturation and function in ?-thalassemia mice and patients. Blood. 2017;129:3087-3099 pubmed publisher..This study provides a mechanistic insight into defective neutrophil maturation in ?-thalassemia patients, which contributes to deficiencies in neutrophil effector functions. ..
- Walsh C, Bestor T. Cytosine methylation and mammalian development. Genes Dev. 1999;13:26-34 pubmed
- Martin L, Douet V, VanWart C, Heller M, Le Saux O. A mouse model of ?-thalassemia shows a liver-specific down-regulation of Abcc6 expression. Am J Pathol. 2011;178:774-83 pubmed publisher..Nevertheless, our result suggested that a similar decrease of ABCC6 expression occurs in the liver of ?-thalassemia patients and may be responsible for their frequent PXE-like manifestations...
- Adamsky K, Weizer O, Amariglio N, Breda L, Harmelin A, Rivella S, et al. Decreased hepcidin mRNA expression in thalassemic mice. Br J Haematol. 2004;124:123-4 pubmed
- Cadiz Rivera B, Fromm G, de Vries C, Fields J, McGrath K, Fiering S, et al. The chromatin "landscape" of a murine adult ?-globin gene is unaffected by deletion of either the gene promoter or a downstream enhancer. PLoS ONE. 2014;9:e92947 pubmed publisher..This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin "landscape" or even by functional assays. ..
- Khandros E, Thom C, D Souza J, Weiss M. Integrated protein quality-control pathways regulate free ?-globin in murine ?-thalassemia. Blood. 2012;119:5265-75 pubmed publisher..Our findings show that multiple interregulated PQC responses degrade excess ?-globin. Therefore, ?-thalassemia fits into the broader framework of protein-aggregation disorders that use PQC pathways as cell-protective mechanisms. ..
- Thongchote K, Svasti S, Teerapornpuntakit J, Krishnamra N, Charoenphandhu N. Running exercise alleviates trabecular bone loss and osteopenia in hemizygous ?-globin knockout thalassemic mice. Am J Physiol Endocrinol Metab. 2014;306:E1406-17 pubmed publisher..In conclusion, BKO mice exhibited pervasive osteopenia and impaired bone microstructure, whereas running exercise appeared to be an effective intervention in alleviating bone microstructural defect in ?-thalassemia. ..
- Rothenberg B, Voland J. beta2 knockout mice develop parenchymal iron overload: A putative role for class I genes of the major histocompatibility complex in iron metabolism. Proc Natl Acad Sci U S A. 1996;93:1529-34 pubmed..As a test of this hypothesis, we predicted that mice which have altered expression of class I gene products, the beta2-microglobulin knockout mice, [beta2m(-/-)], would develop Fe overload...
- Kong Y, Zhou S, Kihm A, Katein A, Yu X, Gell D, et al. Loss of alpha-hemoglobin-stabilizing protein impairs erythropoiesis and exacerbates beta-thalassemia. J Clin Invest. 2004;114:1457-66 pubmed..This function is essential for normal erythropoiesis and, to a greater extent, in beta-thalassemia. Our findings raise the possibility that altered AHSP expression levels could modulate the severity of beta-thalassemia in humans...
- He Z, Russell J. Dynamic posttranscriptional regulation of epsilon-globin gene expression in vivo. Blood. 2007;109:795-801 pubmed
- Yang D, Yu J, Luo Z, Carthy C, Wilson J, Liu Z, et al. Viral myocarditis: identification of five differentially expressed genes in coxsackievirus B3-infected mouse heart. Circ Res. 1999;84:704-12 pubmed..The altered expression of structural and nonstructural genes may play important roles in the mediation of myocarditis development and perhaps other pathological processes in the heart. ..
- Nishino T, Cao H, Stamatoyannopoulos G, Emery D. Effects of human gamma-globin in murine beta-thalassaemia. Br J Haematol. 2006;134:100-8 pubmed
- Bulger M, van Doorninck J, Saitoh N, Telling A, Farrell C, Bender M, et al. Conservation of sequence and structure flanking the mouse and human beta-globin loci: the beta-globin genes are embedded within an array of odorant receptor genes. Proc Natl Acad Sci U S A. 1999;96:5129-34 pubmed
- Brown F, Scott N, Rank G, Collinge J, Vadolas J, Vickaryous N, et al. ENU mutagenesis identifies the first mouse mutants reproducing human ?-thalassemia at the genomic level. Blood Cells Mol Dis. 2013;50:86-92 pubmed publisher..The RBC13 and RBC14 lines are the first ?-thalassemia mouse models that reproduce human ?-thalassemia at the genomic level, and as such highlight the power of ENU mutagenesis screens in generating mouse models of human disease. ..
- Papadopoulos P, GutiÃ©rrez L, Demmers J, Scheer E, Pourfarzad F, Papageorgiou D, et al. TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis. Mol Cell Biol. 2015;35:2103-18 pubmed publisher..Thus, our findings demonstrate a cross talk between canonical TFIID and SAGA complexes and cell-specific transcription activators during development and differentiation. ..
- Russell J, Liebhaber S. Reversal of lethal alpha- and beta-thalassemias in mice by expression of human embryonic globins. Blood. 1998;92:3057-63 pubmed..Moreover, the capacity of embryonic globins to functionally replace their adult homologues brings into question the physiologic basis for globin gene switching. ..
- Casu C, Oikonomidou P, Chen H, Nandi V, Ginzburg Y, Prasad P, et al. Minihepcidin peptides as disease modifiers in mice affected by ?-thalassemia and polycythemia vera. Blood. 2016;128:265-76 pubmed publisher..These studies indicate that drug-like minihepcidins have a potential as future therapeutics for untransfused ?-thalassemia and PV. ..
- Gilman J. Mouse haemoglobin beta chains. Comparative sequence data on adult major and minor beta chains from two species, Mus musculus and Mus cervicolor. Biochem J. 1976;159:43-53 pubmed..K., from whom copies can be obtained on the terms indicated in Biochem. J. (1976) 153, 5. ..
- Kauppi M, Hilton A, Metcalf D, Ng A, Hyland C, Collinge J, et al. Thrombocytopenia and erythrocytosis in mice with a mutation in the gene encoding the hemoglobin ? minor chain. Proc Natl Acad Sci U S A. 2012;109:576-81 pubmed publisher..The Plt12 mouse is a model of high O(2)-affinity hemoglobinopathy and provides insights into hematopoiesis under conditions of chronic hypoxia. ..
- Jahn C, Hutchison C, Phillips S, Weaver S, Haigwood N, Voliva C, et al. DNA sequence organization of the beta-globin complex in the BALB/c mouse. Cell. 1980;21:159-68 pubmed..The rest of this sequence is intact, resembling an adult beta-globin gene except for an inserted base at cocon 90, resulting in a frameshift. Consequently, the beta h3 sequence cannot be translated to produce a normal beta-globin. ..
- Shehee W, Loeb D, Adey N, Burton F, Casavant N, Cole P, et al. Nucleotide sequence of the BALB/c mouse beta-globin complex. J Mol Biol. 1989;205:41-62 pubmed..The significance of these homologies is unclear, but these regions are candidates for further study in functional assays in erythroid cell lines or transgenic animals. ..
- Hug B, Wesselschmidt R, Fiering S, Bender M, Epner E, Groudine M, et al. Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3. Mol Cell Biol. 1996;16:2906-12 pubmed
- Vadolas J, Nefedov M, Wardan H, Mansooriderakshan S, Voullaire L, Jamsai D, et al. Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing mutation. J Biol Chem. 2006;281:7399-405 pubmed..The humanized IVSI-110 mouse model accurately recapitulates the splicing defect found in comparable beta-thalassemia patients. This mouse model is available as a platform for testing strategies for the restoration of normal splicing. ..
- Libani I, Guy E, Melchiori L, Schiro R, Ramos P, Breda L, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood. 2008;112:875-85 pubmed publisher..In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder. ..
- Detloff P, Lewis J, John S, Shehee W, Langenbach R, Maeda N, et al. Deletion and replacement of the mouse adult beta-globin genes by a "plug and socket" repeated targeting strategy. Mol Cell Biol. 1994;14:6936-43 pubmed..One plug deleted 20 kb of DNA containing the two adult beta-globin genes. The other replaced the same region with the human beta-globin gene containing the mutation responsible for sickle cell anemia. ..
- Kautz L, Jung G, Du X, Gabayan V, Chapman J, Nasoff M, et al. Erythroferrone contributes to hepcidin suppression and iron overload in a mouse model of Î²-thalassemia. Blood. 2015;126:2031-7 pubmed publisher..Thus, ERFE mediates hepcidin suppression and contributes to iron overload in a mouse model of Î²-thalassemia. ..
- Rougeon F, Mach B. Cloning and amplification of alpha and beta mouse globin gene sequences synthesised in vitro. Gene. 1977;1:229-39 pubmed..Some of the mouse globin plasmids described contain at least 90% of the globin mRNA sequence and therefore contain the entire translated sequence of the globin genes. Some possible uses of these recombinant plasmids are described. ..
- England S, McGrath K, Frame J, Palis J. Immature erythroblasts with extensive ex vivo self-renewal capacity emerge from the early mammalian fetus. Blood. 2011;117:2708-17 pubmed publisher..Extensively self-renewing erythroblasts, despite their near complete maturity within the hematopoietic hierarchy, may ultimately serve as a renewable source of red cells for transfusion therapy...
- Chen M, Logan T, Hochberg M, Shelat S, Yu X, Wilding G, et al. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction. Blood. 2009;114:4045-53 pubmed publisher..These abnormalities are phenotypically similar to those found in patients with refractory anemia, suggesting that, in some cases, the myelodysplastic syndromes are caused by abnormalities of mitochondrial function. ..
- Voon H, Wardan H, Vadolas J. Co-inheritance of alpha- and beta-thalassaemia in mice ameliorates thalassaemic phenotype. Blood Cells Mol Dis. 2007;39:184-8 pubmed
- May C, Rivella S, Chadburn A, Sadelain M. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood. 2002;99:1902-8 pubmed..These results demonstrate for the first time that viral-mediated globin gene transfer in hematopoietic stem cells effectively treats a severe hemoglobin disorder. ..
- Mucenski M, McLain K, Kier A, Swerdlow S, Schreiner C, Miller T, et al. A functional c-myb gene is required for normal murine fetal hepatic hematopoiesis. Cell. 1991;65:677-89 pubmed..Additional hematopoietic lineages were similarly affected. These results are compatible with a role for c-myb in maintaining the proliferative state of hematopoietic progenitor cells. ..
- Rivella S, May C, Chadburn A, Riviere I, Sadelain M. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer. Blood. 2003;101:2932-9 pubmed..Our findings demonstrate the remarkable efficacy of lentivirus-mediated globin gene transfer in treating a fulminant blood disorder and strongly support the efficacy of gene therapy in the severe hemoglobinopathies. ..
- Trimborn T, Gribnau J, Grosveld F, Fraser P. Mechanisms of developmental control of transcription in the murine alpha- and beta-globin loci. Genes Dev. 1999;13:112-24 pubmed
- Sato J, Shinohara A, Miyashita N, Koshimoto C, Tsuchiya K, Nakahara I, et al. Discovery of a new HBB haplotype w2 in a wild-derived house mouse, Mus musculus. Mamm Genome. 2008;19:155-62 pubmed publisher..Our findings suggest reticulate evolution among the subspecies groups during the evolution of M. musculus. ..
- Storz J, Baze M, Waite J, Hoffmann F, Opazo J, Hayes J. Complex signatures of selection and gene conversion in the duplicated globin genes of house mice. Genetics. 2007;177:481-500 pubmed..The alternative two-locus beta-globin haplotypes are associated with pronounced differences in intraerythrocyte glutathione and nitric oxide metabolism, suggesting a possible mechanism for selection on hemoglobin function. ..
- Yu X, Kong Y, Dore L, Abdulmalik O, Katein A, Zhou S, et al. An erythroid chaperone that facilitates folding of alpha-globin subunits for hemoglobin synthesis. J Clin Invest. 2007;117:1856-65 pubmed..Our findings illustrate what we believe to be a novel adaptive mechanism by which a specialized cell coordinates high-level production of a multisubunit protein and protects against various synthetic imbalances. ..
- Weaver S, Comer M, Jahn C, Hutchison C, Edgell M. The adult beta-globin genes of the "single" type mouse C57BL. Cell. 1981;24:403-11 pubmed..The beta/b dmin gene position is bracketed by a 1450 bp inverted repeat. One of the 1000 bp substitutions maps within this inverted repeat. ..
- He Z, Russell J. Antisickling effects of an endogenous human alpha-like globin. Nat Med. 2004;10:365-7 pubmed
- Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M, et al. Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Genes Dev. 1995;9:2203-13 pubmed..In addition, this result emphasizes that when using homologous recombination to analyze complex regulatory elements in vivo, the inserted selectable marker must be removed to avoid influencing the phenotype of the mutation. ..
- Wu F, Saleem M, Kampik N, Satchwell T, Williamson R, Blattner S, et al. Anion exchanger 1 interacts with nephrin in podocytes. J Am Soc Nephrol. 2010;21:1456-67 pubmed publisher..These data suggest that the podocyte protein kAE1 interacts with nephrin and ILK to maintain the structure and function of the glomerular basement membrane. ..
- Burton F, Loeb D, Chao S, Hutchison C, Edgell M. Transposition of a long member of the L1 major interspersed DNA family into the mouse beta globin gene locus. Nucleic Acids Res. 1985;13:5071-84 pubmed..However, the distance between the two genes flanking this region remains conserved, suggesting that the spacing of the globin genes may be subject to conservative selection. ..