Showing papers by "Andreas Kispert published in 2001"

Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure.

Abstract: Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosomal recessive salt-losing nephropathies. Identification of three genes that code for renal transporters and channels as responsible for aBS has resulted in new insights into renal salt handling, diuretic action and blood-pressure regulation. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deafness (SND) and renal failure, has been mapped to chromosome 1p. We report here the identification by positional cloning, in a region not covered by the human genome sequencing projects, of a new gene, BSND, as the cause of BSND. We examined ten families with BSND and detected seven different mutations in BSND that probably result in loss of function. In accordance with the phenotype, BSND is expressed in the thin limb and the thick ascending limb of the loop of Henle in the kidney and in the dark cells of the inner ear. The gene encodes a hitherto unknown protein with two putative transmembrane alpha-helices and thus might function as a regulator for ion-transport proteins involved in aBS, or else as a new transporter or channel itself.

Gene expression pattern Expression patterns of Wnt genes in mouse gut development

Abstract: Wnt signaling regulates cell fate decisions and cell proliferation during development and in adult tissues in both invertebrates and vertebrates. Here we describe the identification of Wnt genes, Wnt2a, 4, 5a, 5b, 6 and 11, expressed in mouse embryonic gut development. Each of these genes exhibits a characteristic and regional-specific expression pattern along the anterior‐posterior axis of the digestive tube between embryonic day (E) 12.5 and 16.5 of embryonic development. The expression of Wnt5a is confined to the mesenchymal compartment, while expression of Wnt4 is found both in the intestinal epithelium and the mesenteric anlage. Wnt11 is expressed in the epithelium of esophagus and colon, but also in mesenchymal cells of the stomach. Wnt5b and Wnt6 exhibit restricted expression in the epithelium of the esophagus. A characteristic regionalized expression pattern is observed in the developing stomach. Wnt5a is expressed in the mesenchymal layer of the prospective gland region but becomes restricted to the tip of the gland region by E14.5. Wnt11 is highly expressed at the gastroesophageal junctions, while Wnt4 is found in the epithelium lining the pyloric region of the stomach but not in the epithelium of the prospective gland region. q 2001 Elsevier Science Ireland Ltd. All rights reserved.

Gene expression pattern Cloning and expression analysis of the mouse T-box gene Tbx18

Abstract: T-box genes encode transcription factors that regulate a variety of developmental processes. In this report, we describe the cloning andexpression analysis of the novel mouse T-box gene Tbx18. During development expression is most prominent in the proepicardial organ andin the epicardium of the heart. Other sites of expression include the cranial paraxial mesoderm, the presomitic mesoderm, the anterior somitehalf, the genital ridge, and the developing limb buds. q 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Mouse; Embryogenesis; Organogenesis; T-box; Somite; Sclerotome; Septum transversum; Epicardium; Limb; Proepicardial organ 1. ResultsT-box (Tbx) genes encode transcription factors character-ized by a highly related DNA binding region termed T-box(Kispert and Herrmann, 1993; Kispert, 1995). Experimentaland genetic data from different vertebrates including manargue for a key role of Tbx genes in mesoderm formation,patterning and organogenesis (Papaioannou and Silver,1998; Smith, 1999).In order to identify additional members of the mouse Tbxgene family we used a degenerate RT-PCR approach. Oneof the isolated PCR fragments encoded a novel mouse T-box most closely related to a partial human TBX18 cDNA(Yi et al., 1999). Library screening isolated a mouse Tbx18cDNA which is 2761 bases in length and contains a singlelarge open reading frame encoding a protein of 613 aminoacid residues (Fig. 1A).Mouse Tbx18 shows complete sequence conservationwithin the T-box region with the putative translationalproduct of the human TBX18 genomic locus (accessionnumber AL035694), and 94.5% sequence identity over theentire amino acid sequence (data not shown). Within themurine T-box gene family Tbx18 is most closely relatedto the Tbx8/14/15 gene (Agulnik et al., 1998; Wattler etal., 1998). Amino acid sequence conservation amounts to92.8% within the T-box. Phylogenetic analysis clearlyshows that Tbx8 and Tbx18 form a third branch in theTbx1 subfamily of mouse T-box proteins (Fig. 1B).We used in situ hybridization on embryos and sections todetermine the Tbx18 expression pattern (Figs. 2–4). Expres-sion of Tbx18 was detected from embryonic day 7.75(E7.75) on in the segmentally organized somitic, and inthe unsegmented presomitic and cranial paraxial mesoderm(Fig. 2). Tbx18 expression is found in two stripes in thepresomitic mesoderm representing the anterior half of twonewly forming somites (somitomeres) (Fig. 2A–E). Inepithelialized somites Tbx18 expression is restricted to theanterior half where it becomes quickly confined to the scler-otomal compartment (Figs. 2E and 3B,C). Expression ofTbx18 in cranial paraxial mesoderm (Figs. 3B–E,H and4A) and in trunk sclerotome declines after E10.5. Expres-sion in the presomitic mesoderm and in tail somites onlyvanishes after E13.5, after mesoderm formation has come toan end (Fig. 2H–J and data not shown).Tbx18 is very highly expressed in the developing epicar-dium of the heart (Figs. 2B–I and 3B,E,F). The epicardiumis a single cell layer covering the myocardium of the heart,and gives rise to the smooth muscle and endothelial cells ofthe coronary vessels (Mikawa and Fishman, 1992; Mikawaand Gourdie, 1996). Tbx18 expression is first seen in twowings of splanchnic mesoderm caudo-lateral to the hearttube in early E8.25 embryos (Fig. 2B,C). Within hoursthese wings fuse and form a continuous ring of expressionin the septum transversum, a splanchnic mesoderm derivedtissue caudal to the heart (Fig. 2D). A group of grape-likecells in the septum transversum, called proepicardial organstrongly expresses Tbx18 at E9.25 (Figs. 2E and 3B). Thesecells migrate anteriorly over the heart, giving rise to theepicardium (Fig. 2F,G). At E10.5, Tbx18 expression isfound in the epicardium, in the mesothelial lining of the