Based on the map location of the aniridia (AN) locus in human chromosomal band 11p13, we have cloned a candidate AN cDNA (D11S812E) that is completely or partially deleted in two patients with AN. The less than 70 kb smallest region of overlap between the two deletions encompasses the 3' coding region of the cDNA. This cDNA, which spans over 50 kb of genomic DNA, detects a 2.7 kb message specifically within all tissues affected in AN. The predicted polypeptide product possesses a paired domain, a homeodomain, and a serine/threonine-rich carboxy-terminal domain, structural motifs characteristic of certain transcription factors. The concordance between expression and pathology, map location, structure, and predicted function argues that the cDNA corresponds to the AN gene.

We have previously identified two novel members of the fibroblast growth factor receptor (FGFR) gene family expressed in K562 erythroleukemia cells. Here we report cDNA cloning and analysis of one of these genes, named FGFR‐4. The deduced amino acid sequence of FGFR‐4 is 55% identical with both previously characterized FGFRs, flg and bek, and has the structural characteristics of a FGFR family member including three immunoglobulin‐like domains in its extracellular part. Antibodies raised against the carboxy terminus of FGFR‐4 detected 95 and 110 kd glycoproteins with a protein backbone of 88 kd in COS cells transfected with a FGFR‐4 cDNA expression vector. The FGFR‐4 protein expressed in COS cells could also be affinity‐labeled with radioiodinated acidic FGF. Furthermore, ligand binding experiments demonstrated that FGFR‐4 binds acidic FGF with high affinity but does not bind basic FGF. FGFR‐4 is expressed as a 3.0 kb mRNA in the adrenal, lung, kidney, liver, pancreas, intestine, striated muscle and spleen tissues of human fetuses. The expression pattern of FGFR‐4 is distinct from that of flg and bek and the yet additional member of the same gene family, FGFR‐3, which we have also cloned from the K562 leukemia cells. Our results suggest that FGFR‐4 along with other fibroblast growth factor receptors performs cell lineage and tissue‐specific functions.

Abstract. We describe the identification of a novel laminin chain. Overlapping clones were isolated from a human fibrosarcoma HTI080 cell cDNA library spanning a total of 5,200 bp. A second set of clones contained an alternative 3' end sequence giving a total of 4,316 bp. The longer sequence contained an open reading frame for a 1,193-residue-long polypeptide. The alternative sequence was shortened at the carboxylterminal end coding for a 1,111-residue-long polypeptide. The amino acid sequence contained 21 amino acids of a putative signal peptide and 1,172 residues or alternatively 1,090 residues of a sequence with five distinct domains homologous to domains I-V in laminin chains. Comparison of the amino acid sequences showed that the novel laminin chain is homologous to the laminin B2 chain. However, the structure of the novel laminin chain isolated here differs significantly from that of the B2 chain in that it has no domain VI and domains V, IV, and III are shorter, resulting in a truncated laminin chain. The alternative sequence had a shortened domain I/II. In accordance with the current nomenclature, the chain characterized here is termed B2t. Calculation of possible chain interactions of laminin chains with the B2t chain domain I/II indicated that the B2t chain can replace the B2 chain in some laminin molecules. The gene for the laminin B2t chain (LAMB2T) was localized to chromosome lq25-q31 in close proximity to the laminin B2 chain gene. Northern analysis showed that the B2t chain is expressed in several human fetal tissues but differently from the laminin B1 and B2 chains. By in situ hybridization expression of the B2t chain was localized to specific epithelial cells in skin, lung, and kidney as opposed to a general epithelial and endothelial cell expression of the laminin B2 chain in the same tissues.AMININS are large, basement membrane glycoproteins consisting of three chains connected by an u-helical coiled-coil domain. The laminin molecule has a crosslike structure with one long arm and three short arms (69). Laminin, first isolated from a murine Engelbreth-HolmSwarm (EHS) t tumor (70), was shown to be a heterotrimer consisting of one heavy A chain of 400 kD and two light chains, B1 and B2, of ,,o 200 kD each (14). The primary structure of the laminin A, B1, and B2 chains has been determined from mouse (1, 60, 61, 62), man (31,51,53,54), and Drosophila (12,26,48,49). The laminin chains have a characteristic domain structure with internal repeats (2, 3). The short arms are formed of EGF-like modules and globular domains. The long arm is formed by heptad repeats typical for a-helical coiled-coil proteins. Diverse biological functions attributed to laminin include stimulation of cell growth and differentiation, and promotion of neurite outgrowth, cell 1. Abbreviations used in this paper: EHS, Engelbreth-Holm-Swarm; HSPG, heparan sulfate proteoglycan. adhesion, and locomotion. The laminin molecule participates in the assembly of basement membranes through binding to other laminin molecules, type IV coll...

Abstract. The primary structure of the human laminin M chain was determined from cDNA clones isolated from human placental libraries. The clones covered a total of 6,942 bp, with 49-bp encoding a 5' end untranslated region and 6,893-bp coding for a translated sequence. The complete human laminin M chain contains a 22-residue signal peptide and 3,088 residues of the mature M chain. The M chain has a domain structure similar to that of the human and mouse A chains.