Gene Expression Literature Summary

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

Col2a1  collagen, type II, alpha 1   (Synonyms: Col2, Col2a, Col2a-1, Del1, Lpk, M100413, M100856, Rgsc413, Rgsc856)
Results	Reference
1	J:166547 Airik R, Trowe MO, Foik A, Farin HF, Petry M, Schuster-Gossler K, Schweizer M, Scherer G, Kist R, Kispert A, Hydroureternephrosis due to loss of Sox9-regulated smooth muscle cell differentiation of the ureteric mesenchyme. Hum Mol Genet. 2010 Dec 15;19(24):4918-29
1*	J:184022 Aizawa R, Yamada A, Suzuki D, Iimura T, Kassai H, Harada T, Tsukasaki M, Yamamoto G, Tachikawa T, Nakao K, Yamamoto M, Yamaguchi A, Aiba A, Kamijo R, Cdc42 is required for chondrogenesis and interdigital programmed cell death during limb development. Mech Dev. 2012 Mar;129(1-4):38-50
1	J:67299 Arikawa-Hirasawa E, Watanabe H, Takami H, Hassell JR, Yamada Y, Perlecan is essential for cartilage and cephalic development. Nat Genet. 1999 Nov;23(3):354-8
1	J:214677 Bohnenpoll T, Trowe MO, Wojahn I, Taketo MM, Petry M, Kispert A, Canonical Wnt signaling regulates the proliferative expansion and differentiation of fibrocytes in the murine inner ear. Dev Biol. 2014 Jul 1;391(1):54-65
1	J:188176 Caparros-Martin JA, Valencia M, Reytor E, Pacheco M, Fernandez M, Perez-Aytes A, Gean E, Lapunzina P, Peters H, Goodship JA, Ruiz-Perez VL, The ciliary Evc/Evc2 complex interacts with Smo and controls Hedgehog pathway activity in chondrocytes by regulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia. Hum Mol Genet. 2013 Jan 1;22(1):124-39
1*	J:32246 Cheah KS, Lau ET, Au PK, Tam PP, Expression of the mouse alpha 1(II) collagen gene is not restricted to cartilage during development. Development. 1991 Apr;111(4):945-53
1	J:232617 Chen Z, Yue SX, Zhou G, Greenfield EM, Murakami S, ERK1 and ERK2 regulate chondrocyte terminal differentiation during endochondral bone formation. J Bone Miner Res. 2015 May;30(5):765-74
1	J:327334 Choi KY, Lee SW, Park MH, Bae YC, Shin HI, Nam S, Kim YJ, Kim HJ, Ryoo HM, Spatio-temporal expression patterns of Runx2 isoforms in early skeletogenesis. Exp Mol Med. 2002 Dec 31;34(6):426-33
1*	J:288446 Christians A, Weiss AC, Martens H, Klopf MG, Hennies I, Haffner D, Kispert A, Weber RG, Inflammation-like changes in the urothelium of Lifr-deficient mice and LIFR-haploinsufficient humans with urinary tract anomalies. Hum Mol Genet. 2020 May 8;29(7):1192-1204
1	J:107668 Cobb J, Dierich A, Huss-Garcia Y, Duboule D, A mouse model for human short-stature syndromes identifies Shox2 as an upstream regulator of Runx2 during long-bone development. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4511-5
1	J:128902 de Frutos CA, Vega S, Manzanares M, Flores JM, Huertas H, Martinez-Frias ML, Nieto MA, Snail1 is a transcriptional effector of FGFR3 signaling during chondrogenesis and achondroplasias. Dev Cell. 2007 Dec;13(6):872-83
1	J:295760 Felsenthal N, Rubin S, Stern T, Krief S, Pal D, Pryce BA, Schweitzer R, Zelzer E, Development of migrating tendon-bone attachments involves replacement of progenitor populations. Development. 2018 Dec 18;145(24):dev165381
1	J:74145 Gori F, Schipani E, Demay MB, Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development. J Cell Biochem. 2001 Apr 2-27;82(1):46-57
1	J:131986 Han M, Yang X, Lee J, Allan CH, Muneoka K, Development and regeneration of the neonatal digit tip in mice. Dev Biol. 2008 Mar 1;315(1):125-35
1	J:223502 Hata K, Takashima R, Amano K, Ono K, Nakanishi M, Yoshida M, Wakabayashi M, Matsuda A, Maeda Y, Suzuki Y, Sugano S, Whitson RH, Nishimura R, Yoneda T, Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes. Nat Commun. 2013;4:2850
1	J:98426 Hill TP, Spater D, Taketo MM, Birchmeier W, Hartmann C, Canonical Wnt/beta-Catenin Signaling Prevents Osteoblasts from Differentiating into Chondrocytes. Dev Cell. 2005 May;8(5):727-38
1	J:122952 Hung IH, Yu K, Lavine KJ, Ornitz DM, FGF9 regulates early hypertrophic chondrocyte differentiation and skeletal vascularization in the developing stylopod. Dev Biol. 2007 Jul 15;307(2):300-13
1	J:270532 Iezaki T, Fukasawa K, Horie T, Park G, Robinson S, Nakaya M, Fujita H, Onishi Y, Ozaki K, Kanayama T, Hiraiwa M, Kitaguchi Y, Kaneda K, Yoneda Y, Takarada T, Guo XE, Kurose H, Hinoi E, The MAPK Erk5 is necessary for proper skeletogenesis involving a Smurf-Smad-Sox9 molecular axis. Development. 2018 Jul 26;145(14):dev164004
1*	J:54095 Inada M, Yasui T, Nomura S, Miyake S, Deguchi K, Himeno M, Sato M, Yamagiwa H, Kimura T, Yasui N, Ochi T, Endo N, Kitamura Y, Kishimoto T, Komori T, Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999 Apr;214(4):279-90
1*	J:300574 Jiang Q, Qin X, Yoshida CA, Komori H, Yamana K, Ohba S, Hojo H, Croix BS, Kawata-Matsuura VKS, Komori T, Antxr1, Which is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis. Int J Mol Sci. 2020 Mar 31;21(7):2425
1*	J:59287 Karp SJ, Schipani E, St-Jacques B, Hunzelman J, Kronenberg H, McMahon AP, Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development. 2000 Feb;127(3):543-8
1	J:226965 Kato K, Bhattaram P, Penzo-Mendez A, Gadi A, Lefebvre V, SOXC Transcription Factors Induce Cartilage Growth Plate Formation in Mouse Embryos by Promoting Noncanonical WNT Signaling. J Bone Miner Res. 2015 Sep;30(9):1560-71
1	J:298035 Kelly NH, Huynh NPT, Guilak F, Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development. Matrix Biol. 2020 Jul;89:1-10
1	J:104946 Kieslinger M, Folberth S, Dobreva G, Dorn T, Croci L, Erben R, Consalez GG, Grosschedl R, EBF2 regulates osteoblast-dependent differentiation of osteoclasts. Dev Cell. 2005 Dec;9(6):757-67
1	J:128547 Kluppel M, Wight TN, Chan C, Hinek A, Wrana JL, Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development. 2005 Sep;132(17):3989-4003
1	J:317047 Kobayashi T, Papaioannou G, Mirzamohammadi F, Kozhemyakina E, Zhang M, Blelloch R, Chong MW, Early postnatal ablation of the microRNA-processing enzyme, Drosha, causes chondrocyte death and impairs the structural integrity of the articular cartilage. Osteoarthritis Cartilage. 2015 Jul;23(7):1214-20
1	J:124871 Kolpakova-Hart E, Jinnin M, Hou B, Fukai N, Olsen BR, Kinesin-2 controls development and patterning of the vertebrate skeleton by Hedgehog- and Gli3-dependent mechanisms. Dev Biol. 2007 Sep 15;309(2):273-84
1	J:72784 Kovacs CS, Chafe LL, Fudge NJ, Friel JK, Manley NR, Pth regulates fetal blood calcium and skeletal mineralization independently of pthrp. Endocrinology. 2001 Nov;142(11):4983-93
1	J:99514 Kovacs CS, Woodland ML, Fudge NJ, Friel JK, The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E133-44
1*	J:167066 Koyama E, Yasuda T, Minugh-Purvis N, Kinumatsu T, Yallowitz AR, Wellik DM, Pacifici M, Hox11 genes establish synovial joint organization and phylogenetic characteristics in developing mouse zeugopod skeletal elements. Development. 2010 Nov;137(22):3795-800
1	J:202964 Lai LP, Lilley BN, Sanes JR, McMahon AP, Lkb1/Stk11 regulation of mTOR signaling controls the transition of chondrocyte fates and suppresses skeletal tumor formation. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19450-5
1*	J:218168 Lauing KL, Cortes M, Domowicz MS, Henry JG, Baria AT, Schwartz NB, Aggrecan is required for growth plate cytoarchitecture and differentiation. Dev Biol. 2014 Dec 15;396(2):224-36
1	J:193842 Lu C, Wan Y, Cao J, Zhu X, Yu J, Zhou R, Yao Y, Zhang L, Zhao H, Li H, Zhao J, He L, Ma G, Yang X, Yao Z, Guo X, Wnt-mediated reciprocal regulation between cartilage and bone development during endochondral ossification. Bone. 2013 Apr;53(2):566-74
1	J:233282 Maes C, Araldi E, Haigh K, Khatri R, Van Looveren R, Giaccia AJ, Haigh JJ, Carmeliet G, Schipani E, VEGF-independent cell-autonomous functions of HIF-1alpha regulating oxygen consumption in fetal cartilage are critical for chondrocyte survival. J Bone Miner Res. 2012 Mar;27(3):596-609
1	J:296737 Matsuura VKSK, Yoshida CA, Komori H, Sakane C, Yamana K, Jiang Q, Komori T, Expression of a Constitutively Active Form of Hck in Chondrocytes Activates Wnt and Hedgehog Signaling Pathways, and Induces Chondrocyte Proliferation in Mice. Int J Mol Sci. 2020 Apr 12;21(8):2682
1	J:95408 McDonald KR, Fudge NJ, Woodrow JP, Friel JK, Hoff AO, Gagel RF, Kovacs CS, Ablation of calcitonin/calcitonin gene-related peptide-alpha impairs fetal magnesium but not calcium homeostasis. Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E218-26
1*	J:186526 Michikami I, Fukushi T, Honma S, Yoshioka S, Itoh S, Muragaki Y, Kurisu K, Ooshima T, Wakisaka S, Abe M, Trps1 is necessary for normal temporomandibular joint development. Cell Tissue Res. 2012 Apr;348(1):131-40
1	J:182340 Michikami I, Fukushi T, Tanaka M, Egusa H, Maeda Y, Ooshima T, Wakisaka S, Abe M, Kruppel-like factor 4 regulates membranous and endochondral ossification. Exp Cell Res. 2012 Feb 15;318(4):311-25
1	J:210363 Mizuhashi K, Kanamoto T, Moriishi T, Muranishi Y, Miyazaki T, Terada K, Omori Y, Ito M, Komori T, Furukawa T, Filamin-interacting proteins, Cfm1 and Cfm2, are essential for the formation of cartilaginous skeletal elements. Hum Mol Genet. 2014 Jun 1;23(11):2953-67
1*	J:167831 Moffatt P, Lee ER, St-Jacques B, Matsumoto K, Yamaguchi Y, Roughley PJ, Hyaluronan production by means of Has2 gene expression in chondrocytes is essential for long bone development. Dev Dyn. 2011 Feb;240(2):404-12
1	J:74344 Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B, The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002 Jan 11;108(1):17-29
1	J:50292 Naski MC, Colvin JS, Coffin JD, Ornitz DM, Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 1998 Dec;125(24):4977-88
1*	J:14821 Ng LJ, Tam PP, Cheah KS, Preferential expression of alternatively spliced mRNAs encoding type II procollagen with a cysteine-rich amino-propeptide in differentiating cartilage and nonchondrogenic tissues during early mouse development. Dev Biol. 1993 Oct;159(2):403-17
1*	J:38926 Ng LJ, Wheatley S, Muscat GE, Conway-Campbell J, Bowles J, Wright E , Bell DM , Tam PP , Cheah KS , Koopman P, SOX9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev Biol. 1997 Mar 1;183(1):108-21
1	J:137802 Nishioka K, Itoh S, Suemoto H, Kanno S, Gai Z, Kawakatsu M, Tanishima H, Morimoto Y, Hatamura I, Yoshida M, Muragaki Y, Trps1 deficiency enlarges the proliferative zone of growth plate cartilage by upregulation of Pthrp. Bone. 2008 Jul;43(1):64-71
1	J:179841 Pacheco M, Valencia M, Caparros-Martin JA, Mulero F, Goodship JA, Ruiz-Perez VL, Evc works in chondrocytes and osteoblasts to regulate multiple aspects of growth plate development in the appendicular skeleton and cranial base. Bone. 2012 Jan;50(1):28-41
1	J:282858 Ramachandran J, Liu Z, Gray RS, Vokes SA, PRMT5 is necessary to form distinct cartilage identities in the knee and long bone. Dev Biol. 2019 Dec 15;456(2):154-163
1	J:158241 Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M, Nishimura R, Yoneda T, Furuichi T, Ikegawa S, Ikawa M, Okabe M, Imaizumi K, Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat Cell Biol. 2009 Oct;11(10):1197-204
1*	J:334711 Saito S, Mizumoto S, Yonekura T, Yamashita R, Nakano K, Okubo T, Yamada S, Okamura T, Furuichi T, Mice lacking nucleotide sugar transporter SLC35A3 exhibit lethal chondrodysplasia with vertebral anomalies and impaired glycosaminoglycan biosynthesis. PLoS One. 2023;18(4):e0284292
1*	J:39853 Savontaus M, Ihanamaki T, Metsaranta M, Vuorio E, Sandberg-Lall M, Localization of type II collagen mRNA isoforms in the developing eyes of normal and transgenic mice with a mutation in type II collagen gene. Invest Ophthalmol Vis Sci. 1997 Apr;38(5):930-42
1	J:44842 Savontaus M, Metsaranta M, Vuorio E, Mutation in type II collagen gene disturbs spinal development and gene expression patterns in transgenic Del1 mice. Lab Invest. 1997 Dec;77(6):591-600
1*	J:37148 Savontaus M, Metsranta M, Vuorio E, Retarded skeletal development in transgenic mice with a type II collagen mutation. Am J Pathol. 1996 Dec;149(6):2169-82
1*	J:117221 Shibukawa Y, Young B, Wu C, Yamada S, Long F, Pacifici M, Koyama E, Temporomandibular joint formation and condyle growth require Indian hedgehog signaling. Dev Dyn. 2007 Feb;236(2):426-34
1*	J:256718 Shimbo M, Suzuki R, Fuseya S, Sato T, Kiyohara K, Hagiwara K, Okada R, Wakui H, Tsunakawa Y, Watanabe H, Kimata K, Narimatsu H, Kudo T, Takahashi S, Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2. PLoS One. 2017;12(12):e0190333
1	J:194442 Shu B, Zhang M, Xie R, Wang M, Jin H, Hou W, Tang D, Harris SE, Mishina Y, O'Keefe RJ, Hilton MJ, Wang Y, Chen D, BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development. J Cell Sci. 2011 Oct 15;124(Pt 20):3428-40
1	J:163656 Smits P, Bolton AD, Funari V, Hong M, Boyden ED, Lu L, Manning DK, Dwyer ND, Moran JL, Prysak M, Merriman B, Nelson SF, Bonafe L, Superti-Furga A, Ikegawa S, Krakow D, Cohn DH, Kirchhausen T, Warman ML, Beier DR, Lethal skeletal dysplasia in mice and humans lacking the golgin GMAP-210. N Engl J Med. 2010 Jan 21;362(3):206-16
1	J:137353 Sohaskey ML, Yu J, Diaz MA, Plaas AH, Harland RM, JAWS coordinates chondrogenesis and synovial joint positioning. Development. 2008 Jul;135(13):2215-20
1*	J:57297 St-Jacques B, Hammerschmidt M, McMahon AP, Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation [published erratum appears in Genes Dev 1999 Oct 1;13(19):2617]. Genes Dev. 1999 Aug 15;13(16):2072-86
1*	J:134001 Surmann-Schmitt C, Dietz U, Kireva T, Adam N, Park J, Tagariello A, Onnerfjord P, Heinegard D, Schlotzer-Schrehardt U, Deutzmann R, von der Mark K, Stock M, Ucma, a novel secreted cartilage-specific protein with implications in osteogenesis. J Biol Chem. 2008 Mar 14;283(11):7082-93
1	J:154643 Surmann-Schmitt C, Widmann N, Dietz U, Saeger B, Eitzinger N, Nakamura Y, Rattel M, Latham R, Hartmann C, von der Mark H, Schett G, von der Mark K, Stock M, Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis. J Cell Sci. 2009 Oct 15;122(Pt 20):3627-37
1*	J:320535 Suzuki N, Mizuniwa C, Ishii K, Nakagawa Y, Tsuji K, Muneta T, Sekiya I, Akazawa C, Teneurin-4, a transmembrane protein, is a novel regulator that suppresses chondrogenic differentiation. J Orthop Res. 2014 Jul;32(7):915-22
1*	J:296113 Tabe S, Hikiji H, Ariyoshi W, Hashidate-Yoshida T, Shindou H, Shimizu T, Okinaga T, Seta Y, Tominaga K, Nishihara T, Lysophosphatidylcholine acyltransferase 4 is involved in chondrogenic differentiation of ATDC5 cells. Sci Rep. 2017 Dec 1;7(1):16701
1	J:336752 Taieb M, Ghannoum D, Barre L, Ouzzine M, Xylosyltransferase I mediates the synthesis of proteoglycans with long glycosaminoglycan chains and controls chondrocyte hypertrophy and collagen fibers organization of in the growth plate. Cell Death Dis. 2023 Jun 9;14(6):355
1*	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:160473 Trowe MO, Shah S, Petry M, Airik R, Schuster-Gossler K, Kist R, Kispert A, Loss of Sox9 in the periotic mesenchyme affects mesenchymal expansion and differentiation, and epithelial morphogenesis during cochlea development in the mouse. Dev Biol. 2010 Jun 1;342(1):51-62
1	J:94631 Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, McAnally J, Pomajzl C, Shelton JM, Richardson JA, Karsenty G, Olson EN, Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004 Nov 12;119(4):555-66
1	J:48562 Wai AW, Ng LJ, Watanabe H, Yamada Y, Tam PP, Cheah KS, Disrupted expression of matrix genes in the growth plate of the mouse cartilage matrix deficiency (cmd) mutant. Dev Genet. 1998;22(4):349-58
1	J:223511 Wei J, Shimazu J, Makinistoglu MP, Maurizi A, Kajimura D, Zong H, Takarada T, Lezaki T, Pessin JE, Hinoi E, Karsenty G, Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. Cell. 2015 Jun 18;161(7):1576-91
1	J:148141 Wu Q, Chen D, Zuscik MJ, O'Keefe RJ, Rosier RN, Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin. J Bone Miner Res. 2008 Apr;23(4):552-63
1*	J:80668 Yoshida CA, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, Satake M, Takada K, Komori T, Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet. 2002 Dec;32(4):633-8
1*	J:301707 Yoshida CA, Kawane T, Moriishi T, Purushothaman A, Miyazaki T, Komori H, Mori M, Qin X, Hashimoto A, Sugahara K, Yamana K, Takada K, Komori T, Overexpression of Galnt3 in chondrocytes resulted in dwarfism due to the increase of mucin-type O-glycans and reduction of glycosaminoglycans. J Biol Chem. 2014 Sep 19;289(38):26584-96
1	J:89327 Yoshida CA, Yamamoto H, Fujita T, Furuichi T, Ito K, Inoue K, Yamana K, Zanma A, Takada K, Ito Y, Komori T, Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 2004 Apr 15;18(8):952-63
1*	J:28954 Yoshioka H, Iyama K, Inoguchi K, Khaleduzzaman M, Ninomiya Y, Ramirez F, Developmental pattern of expression of the mouse alpha 1 (XI) collagen gene (Col11a1). Dev Dyn. 1995 Sep;204(1):41-7
1	J:238710 Zhang H, Kamiya N, Tsuji T, Takeda H, Scott G, Rajderkar S, Ray MK, Mochida Y, Allen B, Lefebvre V, Hung IH, Ornitz DM, Kunieda T, Mishina Y, Elevated Fibroblast Growth Factor Signaling Is Critical for the Pathogenesis of the Dwarfism in Evc2/Limbin Mutant Mice. PLoS Genet. 2016 Dec;12(12):e1006510
1	J:218833 Zhao H, Zhou W, Yao Z, Wan Y, Cao J, Zhang L, Zhao J, Li H, Zhou R, Li B, Wei G, Zhang Z, French CA, Dekker JD, Yang Y, Fisher SE, Tucker HO, Guo X, Foxp1/2/4 regulate endochondral ossification as a suppresser complex. Dev Biol. 2015 Feb 15;398(2):242-54
1	J:286157 Zheng C, Lin X, Xu X, Wang C, Zhou J, Gao B, Fan J, Lu W, Hu Y, Jie Q, Luo Z, Yang L, Suppressing UPR-dependent overactivation of FGFR3 signaling ameliorates SLC26A2-deficient chondrodysplasias. EBioMedicine. 2019 Feb;40:695-709