TGF β 2 knockout mice have multiple developmental defects that are non-overlapping with other TGF β knockout phenotypes

, SUMMARY The growth and differentiation factor transforming growth factor- β 2 (TGF β 2) is thought to play important roles in multiple developmental processes. Targeted disruption of the TGF β 2 gene was undertaken to determine its essential role in vivo. TGF β 2-null mice exhibit perinatal mortality and a wide range of developmental defects for a single gene disruption. These include cardiac, lung, craniofacial, limb, spinal column, eye, inner ear and urogenital defects. The developmental processes most commonly involved in the affected tissues include epithelial-mesenchymal interactions, cell growth, extracellular matrix production and tissue remodeling. In addition, many affected tissues have neural crest-derived components and simulate neural crest deficiencies. There is no phenotypic overlap with TGF β 1-and TGF β 3-null mice indicating numerous non-compensated functions between the TGF β isoforms.

[1]  B. Hogan,et al.  The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. , 1996, Genes & development.

[2]  J. Rossant,et al.  Mouse mutants and cardiac development: new molecular insights into cardiogenesis. , 1996, Circulation research.

[3]  M. Yin,et al.  Early-onset multifocal inflammation in the transforming growth factor beta 1-null mouse is lymphocyte mediated. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[4]  V. Kaartinen,et al.  Abnormal lung development and cleft palate in mice lacking TGF–β3 indicates defects of epithelial–mesenchymal interaction , 1995, Nature Genetics.

[5]  K. Lyons,et al.  A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. , 1995, Genes & development.

[6]  A. Bradley,et al.  BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. , 1995, Genes & development.

[7]  S. Spicer,et al.  Ultrastructural localization of Na,K-ATPase in the gerbil cochlea. , 1995, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[8]  A. G. Gittenberger-de Groot,et al.  Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment , 1995, The Anatomical record.

[9]  B. Stripp,et al.  Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  K. Herrup,et al.  Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. , 1995, Science.

[11]  J. Martín,et al.  The paired-like homeo box gene MHox is required for early events of skeletogenesis in multiple lineages. , 1995, Genes & development.

[12]  T. Darland,et al.  Role of the transforming growth factor-beta family in the expression of cranial neural crest-specific phenotypes. , 1995, Journal of neurobiology.

[13]  M. Frasch,et al.  Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early Drosophila embryo , 1995, Nature.

[14]  A. Bradley,et al.  Different phenotypes for mice deficient in either activins or activin receptor type II , 1995, Nature.

[15]  R. Jaenisch,et al.  Functional analysis of activins during mammalian development , 1995, Nature.

[16]  A. Copp,et al.  Death before birth: clues from gene knockouts and mutations. , 1995, Trends in genetics : TIG.

[17]  A. G. Gittenberger-de Groot,et al.  Cell origins and tissue boundaries during outflow tract development. , 1995, Trends in cardiovascular medicine.

[18]  C. Sotozono,et al.  Transforming growth factor-beta 1, -beta 2 and -beta 3 mRNA expression in human cornea. , 1995, Current eye research.

[19]  P. Chomczyński,et al.  Substitution of chloroform by bromo-chloropropane in the single-step method of RNA isolation. , 1995, Analytical biochemistry.

[20]  M. C. Johnson,et al.  Toward a molecular understanding of congenital heart disease. , 1995, Circulation.

[21]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (I). Craniofacial and skeletal abnormalities in RAR double mutants. , 1994, Development.

[22]  P. Chambon,et al.  Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. , 1994, Development.

[23]  R. Evans,et al.  RXR alpha mutant mice establish a genetic basis for vitamin A signaling in heart morphogenesis. , 1994, Genes & development.

[24]  R. Maas,et al.  Cloning and developmental expression of the chick type II and type III TGFβ receptors , 1994 .

[25]  N. L. Le Douarin,et al.  Patterning of neural crest derivatives in the avian embryo: in vivo and in vitro studies. , 1993, Developmental biology.

[26]  R. Perris,et al.  The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest. , 1993, Developmental biology.

[27]  P. Chambon,et al.  High postnatal lethality and testis degeneration in retinoic acid receptor alpha mutant mice. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Bodmer The gene tinman is required for specification of the heart and visceral muscles in Drosophila. , 1993, Development.

[29]  P. Nicod,et al.  The Thyroid and the Heart , 1993, Circulation.

[30]  G. Lutty,et al.  Heterogeneity in localization of isoforms of TGF-beta in human retina, vitreous, and choroid. , 1993, Investigative ophthalmology & visual science.

[31]  N M Le Douarin,et al.  The triple origin of skull in higher vertebrates: a study in quail-chick chimeras. , 1993, Development.

[32]  C. Mummery,et al.  RNA and protein localisations of TGF beta 2 in the early mouse embryo suggest an involvement in cardiac development. , 1993, Development.

[33]  M. Sporn,et al.  Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Nadeau,et al.  Mox-1 and Mox-2 define a novel homeobox gene subfamily and are differentially expressed during early mesodermal patterning in mouse embryos. , 1992, Development.

[35]  G. Proetzel,et al.  Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease , 1992, Nature.

[36]  K. Flanders,et al.  Transforming growth factor beta 1 is an epithelial-derived signal peptide that influences otic capsule formation. , 1992, Developmental biology.

[37]  P. McGuire,et al.  Transforming growth factor-beta alters differentiation in cultures of avian neural crest-derived cells: effects on cell morphology, proliferation, fibronectin expression, and melanogenesis. , 1992, Developmental biology.

[38]  K. Flanders,et al.  Localization and binding of transforming growth factor-beta isoforms in mouse preimplantation embryos and in delayed and activated blastocysts. , 1992, Developmental biology.

[39]  Y. Barishak Embryology of the eye and its adnexae. , 1992, Developments in ophthalmology.

[40]  R. Tripathi,et al.  The role of growth factors in the embryogenesis and differentiation of the eye. , 1991, The American journal of anatomy.

[41]  P. Gros,et al.  splotch (Sp2H ), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3 , 1991, Cell.

[42]  H. Moses,et al.  Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development , 1991, The Journal of cell biology.

[43]  M. Sporn,et al.  Localization and actions of transforming growth factor-beta s in the embryonic nervous system. , 1991, Development.

[44]  M. Rudnicki,et al.  Simplified mammalian DNA isolation procedure. , 1991, Nucleic acids research.

[45]  D. Noden Vertebrate craniofacial development: the relation between ontogenetic process and morphological outcome. , 1991, Brain, behavior and evolution.

[46]  C. Mummery,et al.  Differential localization of TGF-beta 2 in mouse preimplantation and early postimplantation development. , 1991, Developmental biology.

[47]  M. Capecchi,et al.  Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5 , 1991, Nature.

[48]  M. Sporn,et al.  Complex regulation of TGF beta expression by retinoic acid in the vitamin A-deficient rat. , 1991, Development.

[49]  L. Birnbaum,et al.  Retinoic acid-induced alterations in the expression of growth factors in embryonic mouse palatal shelves. , 1990, Teratology.

[50]  M. Dickinson,et al.  In situ hybridization analysis of TGF beta 3 RNA expression during mouse development: comparative studies with TGF beta 1 and beta 2. , 1990, Development.

[51]  T. Rosenquist,et al.  Elastogenic Cells in the Developing Cardiovascular System , 1990, Annals of the New York Academy of Sciences.

[52]  P. Deininger Molecular cloning: A laboratory manual , 1990 .

[53]  E. Chen,et al.  Murine transforming growth factor-beta 2 cDNA sequence and expression in adult tissues and embryos. , 1989, Molecular endocrinology.

[54]  M. Sporn,et al.  Some recent advances in the chemistry and biology of transforming growth factor-beta , 1987, The Journal of cell biology.

[55]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[56]  M. Kirby,et al.  Effects of the size of lesions of the cardiac neural crest at various embryonic ages on incidence and type of cardiac defects. , 1986, Circulation.

[57]  Thomas M. Graber,et al.  Factors and mechanisms influencing bone growth , 1983 .

[58]  D. Nichols Neural crest formation in the head of the mouse embryo as observed using a new histological technique. , 1981, Journal of embryology and experimental morphology.

[59]  M J McLeod,et al.  Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. , 1980, Teratology.

[60]  Y. F. Pei,et al.  The prenatal development of the mouse eye , 1970, The Anatomical record.

[61]  C. Bastomsky,et al.  The Thyroid , 1951, The Indian Medical Gazette.

[62]  Topouzis,et al.  Smooth Muscle Lineage Diversity in the Chick Embryo , 1996, Developmental Biology.

[63]  M. Ferguson,et al.  Transforming growth factor-beta 3 is required for secondary palate fusion. , 1995, Nature genetics.

[64]  G. Bennett,et al.  Altered gene expression in murine branchial arches following in utero exposure to retinoic acid. , 1995, Journal of craniofacial genetics and developmental biology.

[65]  D. Kingsley,et al.  The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. , 1994, Genes & development.

[66]  X. F. Wang,et al.  Cloning and developmental expression of the chick type II and type III TGF beta receptors. , 1994, Developmental dynamics : an official publication of the American Association of Anatomists.

[67]  M. Gershon,et al.  Role of growth factors in catecholaminergic expression by neural crest cells: in vitro effects of transforming growth factor beta 1. , 1993, Developmental Dynamics.

[68]  H. Jampel,et al.  Immunolocalization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 in the anterior segment of the human eye. , 1993, Investigative ophthalmology & visual science.

[69]  R. Bachvarova,et al.  Expression of activins and TGF beta 1 and beta 2 RNAs in early postimplantation mouse embryos and uterine decidua. , 1992, Mechanisms of Development.

[70]  P. Schmid,et al.  Differential expression of TGF beta 1, beta 2 and beta 3 genes during mouse embryogenesis. , 1991, Development.

[71]  P. Kondaiah,et al.  Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. , 1991, Development.

[72]  J. Massagué,et al.  The transforming growth factor-beta family. , 1990, Annual review of cell biology.

[73]  C. Mummery,et al.  Expression of transforming growth factor beta 2 during the differentiation of murine embryonal carcinoma and embryonic stem cells. , 1990, Developmental Biology.

[74]  C. A. Thomas,et al.  Molecular cloning. , 1977, Advances in pathobiology.

[75]  N. L. Le Douarin,et al.  Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. , 1975, Journal of embryology and experimental morphology.