title: Genomic organization and chromosomal localization of the mouse IKBKAP gene.
abstract: The autosomal recessive disorder familial dysautonomia (FD) has recently been demonstrated to be caused by mutations in the IKBKAP gene, so named because an initial report suggested that it encoded an IkappaB kinase complex associated protein (IKAP). Two mutations in IKBKAP have been reported to cause FD. The major mutation is a T-->C transition in the donor splice site of intron 20 and the minor mutation is a missense mutation in exon 19 that disrupts a consensus serine/threonine kinase phosphorylation site. We have characterized the cDNA sequences of the mouse, rat and rabbit IKBKAP-encoded mRNAs and determined the genomic organization and chromosomal location of mouse IKBKAP. There is significant homology in the amino acid sequence of IKAP across species and the serine/threonine kinase phosphorylation site altered in the minor FD mutation of IKAP is conserved. The mouse and human IKBKAP genes exhibit significant conservation of their genomic organization and the intron 20 donor splice site sequence, altered in the major FD mutation, is conserved in the human and mouse genes. Mouse IKBKAP is located on the central portion of chromosome 4 and maps to a region in which there is conserved linkage homology between the human and mouse genomes. The homologies observed in the human and mouse sequences should allow, through the process of homologous recombination, for the generation of mice that bear the IKBKAP mutations present in individuals with FD. The characterization of such mice should provide significant information regarding the pathophysiology of FD.
authors.affiliation: Department of Biological Sciences, Laboratory for Familial Dysautonomia Research, Fordham University, Bronx, NY 10458, USA.
authors.forename: R
authors.initials: R
authors.lastname: Coli
authors.forename: S L
authors.initials: SL
authors.lastname: Anderson
authors.forename: S A
authors.initials: SA
authors.lastname: Volpi
authors.forename: B Y
authors.initials: BY
authors.lastname: Rubin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D004247:DNA / Q000737:chemistry / Q000235:genetics; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005260:Female; D005796:Genes / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007438:Introns; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009115:Muridae; D016601:RNA-Binding Proteins; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D035602:Transcriptional Elongation Factors
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; C114720:Elp1 protein, human; C491967:Elp1 protein, rat; C491968:Ikbkap protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D035602:Transcriptional Elongation Factors; D004247:DNA