Gene Expression Literature Summary

• Symbol: Bmpr2
• Name: bone morphogenetic protein receptor type 2
• ID: MGI:1095407

77 matching records from 77 references.

Summary by Age and Assay: Numbers in the table indicate the number of results matching the search criteria.

Age	E0.5	E1	E1.5	E2	E2.5	E3	E4	E4.5	E5.5	E6.5	E7	E7.5	E8.5	E9	E9.5	E10	E10.5	E11.5	E12	E12.5	E13	E13.5	E14	E14.5	E15	E15.5	E16	E16.5	E17	E17.5	E18	E18.5	E19	E19.5	E20	E	P
Immunohistochemistry (section)											1				1			1		1	1	1		1	1	2				1	1	1	1	1			5
In situ RNA (section)										1		1	1	3		1	1	4	1	4		3		9	2	4	1	3		1		1					5
In situ RNA (whole mount)								1	1	2	1	2	1	1	1	1	1	1		2		2														1	1
Western blot														1					1	1	1	1		1	1	2	1		1	1	1	1	1	1			7
RT-PCR	1	1	1	2	1	1	1			1	1	1			4	1	1	3	1	3	3	5	3	9	4	1	3	5	2	5	3	5	1	1	1	2	13
cDNA clones																																					3
RNase protection																																					1

Summary by Gene and Reference: Number indicates the number of results matching the search criteria recorded for each reference.
* Indicates detailed expression data entries available

Bmpr2  bone morphogenetic protein receptor type 2   (Synonyms: 2610024H22Rik, BMP-2, BMPRII, BMPR-II)
Results	Reference
1	J:226941 Akerberg BN, Sarangam ML, Stankunas K, Endocardial Brg1 disruption illustrates the developmental origins of semilunar valve disease. Dev Biol. 2015 Nov 1;407(1):158-72
9*	J:125495 Alejandre-Alcazar MA, Shalamanov PD, Amarie OV, Sevilla-Perez J, Seeger W, Eickelberg O, Morty RE, Temporal and spatial regulation of bone morphogenetic protein signaling in late lung development. Dev Dyn. 2007 Oct;236(10):2825-35
1*	J:313619 Bedogni F, Hevner RF, Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development. Front Mol Neurosci. 2021;14:686034
3	J:61931 Beppu H, Kawabata M, Hamamoto T, Chytil A, Minowa O, Noda T, Miyazono K, BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol. 2000 May 1;221(1):249-58
1	J:202725 Borges L, Iacovino M, Koyano-Nakagawa N, Baik J, Garry DJ, Kyba M, Perlingeiro RC, Expression levels of endoglin distinctively identify hematopoietic and endothelial progeny at different stages of yolk sac hematopoiesis. Stem Cells. 2013 Sep;31(9):1893-901
1	J:239780 Caputo L, Witzel HR, Kolovos P, Cheedipudi S, Looso M, Mylona A, van IJcken WF, Laugwitz KL, Evans SM, Braun T, Soler E, Grosveld F, Dobreva G, The Isl1/Ldb1 Complex Orchestrates Genome-wide Chromatin Organization to Instruct Differentiation of Multipotent Cardiac Progenitors. Cell Stem Cell. 2015 Sep 03;17(3):287-99
8*	J:148775 Danesh SM, Villasenor A, Chong D, Soukup C, Cleaver O, BMP and BMP receptor expression during murine organogenesis. Gene Expr Patterns. 2009 Jun;9(5):255-65
1	J:317152 Dehghan Z, Mohammadi-Yeganeh S, Rezaee D, Salehi M, MicroRNA-21 is involved in oocyte maturation, blastocyst formation, and pre-implantation embryo development. Dev Biol. 2021 Dec;480:69-77
1	J:80024 Delot EC, Bahamonde ME, Zhao M, Lyons KM, BMP signaling is required for septation of the outflow tract of the mammalian heart. Development. 2003 Jan;130(1):209-20
1	J:108241 Desai J, Shannon ME, Johnson MD, Ruff DW, Hughes LA, Kerley MK, Carpenter DA, Johnson DK, Rinchik EM, Culiat CT, Nell1-deficient mice have reduced expression of extracellular matrix proteins causing cranial and vertebral defects. Hum Mol Genet. 2006 Apr 15;15(8):1329-41
2	J:329048 Deuper L, Meuser M, Thiesler H, Jany UWH, Rudat C, Hildebrandt H, Trowe MO, Kispert A, Mesenchymal FGFR1 and FGFR2 control patterning of the ureteric mesenchyme by balancing SHH and BMP4 signaling. Development. 2022 Sep 1;149(17):dev200767
7*	J:82773 Dichmann DS, Miller CP, Jensen J, Scott Heller R, Serup P, Expression and misexpression of members of the FGF and TGFbeta families of growth factors in the developing mouse pancreas. Dev Dyn. 2003 Apr;226(4):663-74
1*	J:153498 Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I, Lin-Marq N, Koch M, Bilio M, Cantiello I, Verde R, De Masi C, Bianchi SA, Cicchini J, Perroud E, Mehmeti S, Dagand E, Schrinner S, Nurnberger A, SchmidtK, Metz K, Zwingmann C, Brieske N, Springer C, Hernandez AM, Herzog S, Grabbe F, Sieverding C, Fischer B, Schrader K, Brockmeyer M, Dettmer S, Helbig C, Alunni V, Battaini MA, Mura C, Henrichsen CN, Garcia-Lopez R, Echevarria D, Puelles E, et al., A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol. 2011;9(1):e1000582
1	J:119289 Dudas M, Kim J, Li WY, Nagy A, Larsson J, Karlsson S, Chai Y, Kaartinen V, Epithelial and ectomesenchymal role of the type I TGF-beta receptor ALK5 during facial morphogenesis and palatal fusion. Dev Biol. 2006 Aug 15;296(2):298-314
1*	J:130860 Durand C, Robin C, Bollerot K, Baron MH, Ottersbach K, Dzierzak E, Embryonic stromal clones reveal developmental regulators of definitive hematopoietic stem cells. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20838-43
2*	J:206541 Engelhard C, Sarsfield S, Merte J, Wang Q, Li P, Beppu H, Kolodkin AL, Sucov HM, Ginty DD, MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. Elife. 2013;2:e01160
2	J:77444 Faber SC, Robinson ML, Makarenkova HP, Lang RA, Bmp signaling is required for development of primary lens fiber cells. Development. 2002 Aug;129(15):3727-37
1	J:192165 Forsman CL, Ng BC, Heinze RK, Kuo C, Sergi C, Gopalakrishnan R, Yee D, Graf D, Schwertfeger KL, Petryk A, BMP-binding protein twisted gastrulation is required in mammary gland epithelium for normal ductal elongation and myoepithelial compartmentalization. Dev Biol. 2013 Jan 1;373(1):95-106
2	J:175737 Gamer LW, Tsuji K, Cox K, Capelo LP, Lowery J, Beppu H, Rosen V, BMPR-II is dispensable for formation of the limb skeleton. Genesis. 2011 Sep;49(9):719-24
1*	J:80062 Hager-Theodorides AL, Outram SV, Shah DK, Sacedon R, Shrimpton RE, Vicente A, Varas A, Crompton T, Bone morphogenetic protein 2/4 signaling regulates early thymocyte differentiation. J Immunol. 2002 Nov 15;169(10):5496-504
1	J:93248 Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MS, Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet. 2004 Nov 1;13(19):2263-78
1	J:79513 Hayashi K, Kobayashi T, Umino T, Goitsuka R, Matsui Y, Kitamura D, SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast. Mech Dev. 2002 Oct;118(1-2):99
2	J:309228 Hill C, Jacobs B, Kennedy L, Rohde S, Zhou B, Baldwin S, Goudy S, Cranial neural crest deletion of VEGFa causes cleft palate with aberrant vascular and bone development. Cell Tissue Res. 2015 Sep;361(3):711-22
2*	J:218259 Hill CR, Jacobs BH, Brown CB, Barnett JV, Goudy SL, Type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis. Dev Dyn. 2015 Feb;244(2):122-33
3	J:207974 Hill CR, Yuasa M, Schoenecker J, Goudy SL, Jagged1 is essential for osteoblast development during maxillary ossification. Bone. 2014 May;62:10-21
1*	J:231083 Hines EA, Verheyden JM, Lashua AJ, Larson SC, Branchfield K, Domyan ET, Gao J, Harvey JF, Herriges JC, Hu L, Mcculley DJ, Throckmorton K, Yokoyama S, Ikeda A, Xu G, Sun X, Syndactyly in a novel Fras1(rdf) mutant results from interruption of signals for interdigital apoptosis. Dev Dyn. 2016 Apr;245(4):497-507
3	J:99699 Jiang FX, Harrison LC, Convergence of bone morphogenetic protein and laminin-1 signaling pathways promotes proliferation and colony formation by fetal mouse pancreatic cells. Exp Cell Res. 2005 Aug 1;308(1):114-22
1	J:257633 Jiang FX, Harrison LC, Transient Impairment of Islet Architectural Development in Pancreas-Specific Bmpr1a-Deleted Prenatal Mice Involves Reduced Expression of E-Cadherin. Stem Cells Dev. 2017 Dec 1;26(23):1706-1714
1	J:143588 Kamiya N, Ye L, Kobayashi T, Mochida Y, Yamauchi M, Kronenberg HM, Feng JQ, Mishina Y, BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008 Nov;135(22):3801-11
6*	J:168597 Kashimada K, Pelosi E, Chen H, Schlessinger D, Wilhelm D, Koopman P, FOXL2 and BMP2 act cooperatively to regulate follistatin gene expression during ovarian development. Endocrinology. 2011 Jan;152(1):272-80
2*	J:210876 Knosp WM, Scott V, Bachinger HP, Stadler HS, HOXA13 regulates the expression of bone morphogenetic proteins 2 and 7 to control distal limb morphogenesis. Development. 2004 Sep;131(18):4581-92
1	J:184521 Koss M, Bolze A, Brendolan A, Saggese M, Capellini TD, Bojilova E, Boisson B, Prall OW, Elliott DA, Solloway M, Lenti E, Hidaka C, Chang CP, Mahlaoui N, Harvey RP, Casanova JL, Selleri L, Congenital Asplenia in Mice and Humans with Mutations in a Pbx/Nkx2-5/p15 Module. Dev Cell. 2012 May 15;22(5):913-26
2	J:313922 Kuiper-Makris C, Zanetti D, Vohlen C, Fahle L, Muller M, Odenthal M, Felderhoff-Muser U, Dotsch J, Alejandre Alcazar MA, Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function. Sci Rep. 2020 Dec 28;10(1):22395
1	J:217820 Larabee SM, Coia H, Jones S, Cheung E, Gallicano GI, miRNA-17 Members that Target Bmpr2 Influence Signaling Mechanisms Important for Embryonic Stem Cell Differentiation In Vitro and Gastrulation in Embryos. Stem Cells Dev. 2015 Feb 1;24(3):354-71
1	J:142576 Lebeurrier N, Launay S, Macrez R, Maubert E, Legros H, Leclerc A, Jamin SP, Picard JY, Marret S, Laudenbach V, Berger P, Sonderegger P, Ali C, di Clemente N, Vivien D, Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin. J Cell Sci. 2008 Oct 15;121(Pt 20):3357-65
1	J:316198 Lei R, Zhang K, Liu K, Shao X, Ding Z, Wang F, Hong Y, Zhu M, Li H, Li H, Transferrin receptor facilitates TGF-beta and BMP signaling activation to control craniofacial morphogenesis. Cell Death Dis. 2016 Jun 30;7(6):e2282
1	J:161852 Libusova L, Stemmler MP, Hierholzer A, Schwarz H, Kemler R, N-cadherin can structurally substitute for E-cadherin during intestinal development but leads to polyp formation. Development. 2010 Jul;137(14):2297-305
1	J:337546 Liu H, Lu P, He S, Luo Y, Fang Y, Benkaci S, Wu B, Wang Y, Zhou B, beta-Catenin regulates endocardial cushion growth by suppressing p21. Life Sci Alliance. 2023 Sep;6(9)
7	J:251646 Liu J, Saito K, Maruya Y, Nakamura T, Yamada A, Fukumoto E, Ishikawa M, Iwamoto T, Miyazaki K, Yoshizaki K, Ge L, Fukumoto S, Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation. Sci Rep. 2016 Mar 31;6:23670
4	J:82686 Liu J, Wilson S, Reh T, BMP receptor 1b is required for axon guidance and cell survival in the developing retina. Dev Biol. 2003 Apr 1;256(1):34-48
3	J:195172 Ludtke TH, Farin HF, Rudat C, Schuster-Gossler K, Petry M, Barnett P, Christoffels VM, Kispert A, Tbx2 controls lung growth by direct repression of the cell cycle inhibitor genes Cdkn1a and Cdkn1b. PLoS Genet. 2013 Jan;9(1):e1003189
1	J:238888 Luo W, Zhao X, Jin H, Tao L, Zhu J, Wang H, Hemmings BA, Yang Z, Akt1 signaling coordinates BMP signaling and beta-catenin activity to regulate second heart field progenitor development. Development. 2015 Feb 15;142(4):732-42
3*	J:162220 Magdaleno S, Jensen P, Brumwell CL, Seal A, Lehman K, Asbury A, Cheung T, Cornelius T, Batten DM, Eden C, Norland SM, Rice DS, Dosooye N, Shakya S, Mehta P, Curran T, BGEM: an in situ hybridization database of gene expression in the embryonic and adult mouse nervous system. PLoS Biol. 2006 Apr;4(4):e86
7*	J:219314 Mao S, Li H, Sun Q, Zen K, Zhang CY, Li L, miR-17 regulates the proliferation and differentiation of the neural precursor cells during mouse corticogenesis. FEBS J. 2014 Feb;281(4):1144-58
4	J:74197 Martinez G, Loveland KL, Clark AT, Dziadek M, Bertram JF, Expression of bone morphogenetic protein receptors in the developing mouse metanephros. Exp Nephrol. 2001;9(6):372-9
4*	J:257654 Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J, Sundstrom E, Pachnis V, Marklund U, Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System. Gastroenterology. 2018 Feb;154(3):624-636
2*	J:103164 Minina E, Schneider S, Rosowski M, Lauster R, Vortkamp A, Expression of Fgf and Tgfbeta signaling related genes during embryonic endochondral ossification. Gene Expr Patterns. 2005 Dec;6(1):102-109
2*	J:83431 Morgan EA, Nguyen SB, Scott V, Stadler HS, Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia. Development. 2003 Jul;130(14):3095-109
1	J:261627 Mori K, Nakamura H, Kurooka H, Miyachi H, Tamada K, Sugai M, Takumi T, Yokota Y, Id2 determines intestinal identity through repression of the foregut transcription factor, Irx5. Mol Cell Biol. 2018 Feb 20;
10	J:106095 Nadiri A, Kuchler-Bopp S, Perrin-Schmitt F, Lesot H, Expression patterns of BMPRs in the developing mouse molar. Cell Tissue Res. 2006 Apr;324(1):33-40
3	J:201437 Nagashima T, Li Q, Clementi C, Lydon JP, DeMayo FJ, Matzuk MM, BMPR2 is required for postimplantation uterine function and pregnancy maintenance. J Clin Invest. 2013 Jun 3;123(6):2539-50
2	J:166960 Ohta S, Mansour SL, Schoenwolf GC, BMP/SMAD signaling regulates the cell behaviors that drive the initial dorsal-specific regional morphogenesis of the otocyst. Dev Biol. 2010 Nov 15;347(2):369-81
5	J:205042 Osorio C, Chacon PJ, Kisiswa L, White M, Wyatt S, Rodriguez-Tebar A, Davies AM, Growth differentiation factor 5 is a key physiological regulator of dendrite growth during development. Development. 2013 Dec;140(23):4751-62
2*	J:108109 Oxburgh L, Chu GC, Michael SK, Robertson EJ, TGFbeta superfamily signals are required for morphogenesis of the kidney mesenchyme progenitor population. Development. 2004 Sep;131(18):4593-605
1	J:147287 Retting KN, Song B, Yoon BS, Lyons KM, BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development. 2009 Apr;136(7):1093-104
17*	J:42540 Roelen BA, Goumans MJ, van Rooijen MA, Mummery CL, Differential expression of BMP receptors in early mouse development. Int J Dev Biol. 1997 Aug;41(4):541-9
1*	J:277331 Sah RK, Yang A, Bah FB, Adlat S, Bohio AA, Oo ZM, Wang C, Myint MZZ, Bahadar N, Zhang L, Feng X, Zheng Y, Transcriptome profiling of mouse brain and lung under Dip2a regulation using RNA-sequencing. PLoS One. 2019;14(7):e0213702
1	J:205755 Sakaguchi M, Sharmin S, Taguchi A, Ohmori T, Fujimura S, Abe T, Kiyonari H, Komatsu Y, Mishina Y, Asashima M, Araki E, Nishinakamura R, The phosphatase Dullard negatively regulates BMP signalling and is essential for nephron maintenance after birth. Nat Commun. 2013;4:1398
1	J:270543 Tanahashi H, Suzuki T, Deletion of Lrp4 increases the incidence of microphthalmia. Biochem Biophys Res Commun. 2018 Nov 30;506(3):478-484
2*	J:174767 Tang F, Barbacioru C, Nordman E, Bao S, Lee C, Wang X, Tuch BB, Heard E, Lao K, Surani MA, Deterministic and stochastic allele specific gene expression in single mouse blastomeres. PLoS One. 2011;6(6):e21208
5*	J:215487 Thompson CL, Ng L, Menon V, Martinez S, Lee CK, Glattfelder K, Sunkin SM, Henry A, Lau C, Dang C, Garcia-Lopez R, Martinez-Ferre A, Pombero A, Rubenstein JL, Wakeman WB, Hohmann J, Dee N, Sodt AJ, Young R, Smith K, Nguyen TN, Kidney J, Kuan L, Jeromin A,Kaykas A, Miller J, Page D, Orta G, Bernard A, Riley Z, Smith S, Wohnoutka P, Hawrylycz MJ, Puelles L, Jones AR, A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain. Neuron. 2014 Jul 16;83(2):309-23
1	J:242253 Tian E, Stevens SR, Guan Y, Springer DA, Anderson SA, Starost MF, Patel V, Ten Hagen KG, Tabak LA, Galnt1 is required for normal heart valve development and cardiac function. PLoS One. 2015;10(1):e0115861
1	J:171333 Tilleman H, Hakim V, Novikov O, Liser K, Nashelsky L, Di Salvio M, Krauthammer M, Scheffner O, Maor I, Mayseless O, Meir I, Kayam G, Sela-Donenfeld D, Simeone A, Brodski C, Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons. Mol Cell Neurosci. 2010 Sep;45(1):1-11
1	J:87765 Timmerman LA, Grego-Bessa J, Raya A, Bertran E, Perez-Pomares JM, Diez J, Aranda S, Palomo S, McCormick F, Izpisua-Belmonte JC, de la Pompa JL, Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 2004 Jan 1;18(1):99-115
1	J:245879 Tischfield MA, Robson CD, Gilette NM, Chim SM, Sofela FA, DeLisle MM, Gelber A, Barry BJ, MacKinnon S, Dagi LR, Nathans J, Engle EC, Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura. Dev Cell. 2017 Sep 11;42(5):445-461.e5
4	J:147082 Torihashi S, Hattori T, Hasegawa H, Kurahashi M, Ogaeri T, Fujimoto T, The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut. Differentiation. 2009 Mar;77(3):277-89
3	J:235682 Villacorte M, Delmarcelle AS, Lernoux M, Bouquet M, Lemoine P, Bolsee J, Umans L, de Sousa Lopes SC, Van Der Smissen P, Sasaki T, Bommer G, Henriet P, Refetoff S, Lemaigre FP, Zwijsen A, Courtoy PJ, Pierreux CE, Thyroid follicle development requires Smad1/5- and endothelial cell-dependent basement membrane assembly. Development. 2016 Jun 1;143(11):1958-70
1	J:278336 Wang W, Chun H, Baek J, Sadik JE, Shirazyan A, Razavi P, Lopez N, Lyons KM, The TGFbeta type I receptor TGFbetaRI functions as an inhibitor of BMP signaling in cartilage. Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15570-15579
1	J:199879 Wang Y, Wu B, Chamberlain AA, Lui W, Koirala P, Susztak K, Klein D, Taylor V, Zhou B, Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development. PLoS One. 2013;8(4):e60244
1	J:341382 Wu B, Wu B, Benkaci S, Shi L, Lu P, Park T, Morrow BE, Wang Y, Zhou B, Crk and Crkl Are Required in the Endocardial Lineage for Heart Valve Development. J Am Heart Assoc. 2023 Sep 19;12(18):e029683
1	J:137730 Wu M, Li J, Engleka KA, Zhou B, Lu MM, Plotkin JB, Epstein JA, Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice. J Clin Invest. 2008 Jun;118(6):2076-87
1	J:187117 Xu J, Qi X, Gong J, Yu M, Zhang F, Sha H, Gao X, Fstl1 antagonizes BMP signaling and regulates ureter development. PLoS One. 2012;7(4):e32554
3	J:146156 Yamamoto M, Beppu H, Takaoka K, Meno C, Li E, Miyazono K, Hamada H, Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo. J Cell Biol. 2009 Jan 26;184(2):323-34
8	J:47045 Zhang D, Mehler MF, Song Q, Kessler JA, Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression. J Neurosci. 1998 May 1;18(9):3314-26
6*	J:332879 Zheng J, Liu H, Yu M, Lin B, Sun K, Liu H, Feng H, Liu Y, Han D, BMPR2 Variants Underlie Nonsyndromic Oligodontia. Int J Mol Sci. 2023 Jan 13;24(2)
2	J:315014 Zhou C, Chen D, Ren J, Huang D, Li R, Luo H, Guan C, Cao Y, Wang W, FGF8 and BMP2 mediated dynamic regulation of dental mesenchyme proliferation and differentiation via Lhx8/Suv39h1 complex. J Cell Mol Med. 2021 Mar;25(6):3051-3062
1	J:197419 Zhou Y, Tanzie C, Yan Z, Chen S, Duncan M, Gaudenz K, Li H, Seidel C, Lewis B, Moran A, Libby RT, Kiernan AE, Xie T, Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye. Proc Natl Acad Sci U S A. 2013 May 28;110(22):8966-71