RESUMO
We have determined the sequence and structure of the mouse Müllerian-inhibiting substance (MIS) type II receptor gene. Sequence comparisons demonstrate that the mouse, rat, rabbit, and human MIS type II receptors are highly conserved. The mouse MIS type II receptor gene is encoded by 11 exons and spans approximately 9-kb. Only half of the intron/exon boundaries of its kinase domain are conserved in comparison to the kinase domain of the related activin type II receptor. Whereas the activin type II receptor gene contains large introns (> 40-kb), the largest intron of the MIS type II receptor gene is only 4.3-kb. The MIS type II receptor gene (Amhr) is closely linked to Hoxc on mouse chromosome 15. Knowledge of the sequence and genomic structure of Amhr provides important information for the genetic manipulation of the Amhr locus.
Assuntos
Mapeamento Cromossômico , Camundongos/genética , Receptores de Peptídeos/química , Receptores de Peptídeos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sequência Consenso , Sequência Conservada , Éxons , Humanos , Íntrons , Dados de Sequência Molecular , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Coelhos , Ratos , Receptores de Peptídeos/biossíntese , Receptores de Fatores de Crescimento Transformadores beta , Mapeamento por Restrição , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
The amiloride-sensitive epithelial sodium channel alpha, beta, and gamma subunit genes, Scnn1a, Scnn1b, and Scnn1g, and the thiazide-sensitive sodium chloride cotransporter gene, Slc12a1, have been mapped in the mouse using an interspecific backcross panel. These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping.
Assuntos
Proteínas de Transporte/genética , Canais de Sódio/genética , Simportadores , Animais , Mapeamento Cromossômico , Genes , Ligação Genética , Camundongos , Camundongos Endogâmicos C57BL , Muridae , Simportadores de Cloreto de SódioRESUMO
The Na/H exchanger genes Slc9a1, Slc9a2, Slc9a3, and Slc9a4 have been mapped in the mouse using an interspecific backcross panel. These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping.
Assuntos
Mapeamento Cromossômico , Trocadores de Sódio-Hidrogênio/genética , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The products of five distinct loci, Egf, Tgfa, Areg, Btc, and Hegfl act as ligands for the epidermal growth factor receptor. Egf and Tgfa have previously been mapped to mouse chromosomes 3 and 6, respectively, but the mouse chromosomal locations of Areg, Btc, and Hegfl have not been reported. Here, we show that Areg and Btc are tightly linked on mouse chromosome 5, while Hegfl maps to mouse chromosome 18. We also provide evidence that a putative sixth family member, Sdgf, is in fact a species variant of Areg. These results confirm and extend known relationships between mouse and human chromosomes, and they also provide new information regarding the evolution of this important gene family.
Assuntos
Fator de Crescimento Epidérmico/genética , Receptores ErbB/metabolismo , Glicoproteínas/genética , Substâncias de Crescimento/genética , Peptídeos e Proteínas de Sinalização Intercelular , Anfirregulina , Animais , Betacelulina , Mapeamento Cromossômico , Família de Proteínas EGF , Fator de Crescimento Epidérmico/metabolismo , Ligação Genética , Glicoproteínas/metabolismo , Substâncias de Crescimento/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Ligantes , CamundongosRESUMO
The Na,K-ATPase is an integral plasma membrane protein consisting of alpha and beta subunits, each of which has discrete isoforms expressed in a tissue-specific manner. Of the three functional alpha isoform genes, the one encoding the alpha 3 isoform is the most tissue-restricted in its expression, being found primarily in the brain. To identify regions of the alpha 3 isoform gene that are involved in directing expression in the brain, a 1.6 kb 5'-flanking sequence was attached to a reporter gene, chloramphenicol acetyltransferase (CAT). The alpha 3-CAT chimeric gene construct was microinjected into fertilized mouse eggs, and transgenic mice were produced. Analysis of adult transgenic mice from different lines revealed that the transgene is expressed primarily in the brain. To further delineate regions that are needed for conferring expression in this tissue, systematic deletions of the 5'-flanking sequence of the alpha 3-CAT fusion constructs were made and analyzed, again using transgenic mice. The results from these analyses indicate that DNA sequences required for mediating brain-specific expression of the alpha 3 isoform gene are present within 210 bp upstream of the transcription initiation site. alpha 3-CAT promoter constructs containing scanning mutations in this region were also assayed in transgenic mice. These studies have identified both a functional neural-restrictive silencer element as well as a positively acting cis element.
Assuntos
Encéfalo/enzimologia , Regulação Enzimológica da Expressão Gênica/genética , Sequências Reguladoras de Ácido Nucleico/genética , ATPase Trocadora de Sódio-Potássio/genética , Animais , Sequência de Bases , Isoenzimas/química , Isoenzimas/genética , Camundongos , Camundongos Transgênicos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Especificidade de Órgãos , RNA Mensageiro/biossíntese , Ratos , Proteínas Recombinantes de Fusão/biossíntese , Deleção de Sequência/fisiologia , ATPase Trocadora de Sódio-Potássio/químicaAssuntos
Glicosídeos Cardíacos/metabolismo , Regulação Enzimológica da Expressão Gênica , Isoenzimas/genética , ATPase Trocadora de Sódio-Potássio/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Isoenzimas/metabolismo , Dados de Sequência Molecular , ATPase Trocadora de Sódio-Potássio/análise , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Genomic clones containing the 5'-flanking region and exon 1 of the human and rat Na,K-ATPase alpha 3 isoform gene have been isolated and characterized. The nucleotide sequences of 1.6 kb of the rat gene and 2.8 kb of the human gene in the 5'-flanking region were determined. Mapping of transcription initiation sites by primer extension and S1 nuclease protection analyses indicates that transcription is initiated in the same region in both genes although the rat gene has a greater number of initiation sites. Neither gene has a canonical TATA box, having instead a ATAT sequence preceding the transcription initiation sites. There is a perfect CCAAT sequence, in the reverse orientation, approximately 30 bp upstream of the potential TATA box in both genes. We have identified potential binding sites for transcription factors Sp-1, AP-1, AP-2, and AP-4, as well as for glucocorticoid and thyroid hormone receptors in the 5'-flanking regions. These are conserved in both human and rat alpha 3 isoform genes.
