Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.

Shen, Anna L; Moran, Susan A; Glover, Edward A; Drinkwater, Norman R; Swearingen, Rebecca E; Teixeira, Leandro B; Bradfield, Christopher A

Shen, Anna L; Moran, Susan A; Glover, Edward A; Drinkwater, Norman R; Swearingen, Rebecca E; Teixeira, Leandro B; Bradfield, Christopher A.

Afiliación

Shen AL; The McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
Moran SA; McPherson Eye Research Institute, University of Wisconsin, Madison, Wisconsin, United States of America.
Glover EA; The McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
Drinkwater NR; The McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
Swearingen RE; The McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
Teixeira LB; The McArdle Laboratory for Cancer Research, Department of Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, United States of America.
Bradfield CA; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, United States of America.

PLoS One ; 11(6): e0157577, 2016.

Article en En | MEDLINE | ID: mdl-27310661

RESUMEN

We have previously described a mouse model of human posterior polymorphous corneal dystrophy (PPCD) and localized the causative mutation to a 6.2 Mbp region of chromosome 2, termed Ppcd1. We now show that the gene rearrangement linked to mouse Ppcd1 is a 3.9 Mbp chromosomal inversion flanked by 81 Kbp and 542 bp deletions. This recombination event leads to deletion of Csrp2bp Exons 8 through 11, Dzank1 Exons 20 and 21, and the pseudogene Znf133. In addition, we identified translocation of novel downstream sequences to positions adjacent to Csrp2bp Exon 7 and Dzank1 Exon 20. Twelve novel fusion transcripts involving Csrp2bp or Dzank1 linked to downstream sequences have been identified. Eight are expressed at detectable levels in PPCD1 but not wildtype eyes. Upregulation of two Csrp2bp fusion transcripts, as well as upregulation of the adjacent gene, Ovol2, was observed. Absence of the PPCD1 phenotype in animals haploinsufficient for Csrp2bp or both Csrp2bp and Dzank1 rules out haploinsufficiency of these genes as a cause of mouse PPCD1. Complementation experiments confirm that PPCD1 embryonic lethality is due to disruption of Csrp2bp expression. The ocular expression pattern of Csrp2bp is consistent with a role for this protein in corneal development and pathogenesis of PPCD1.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/genética; Proteínas Portadoras/genética; Cromosomas de los Mamíferos/química; Distrofias Hereditarias de la Córnea/genética; Reordenamiento Génico; Histona Acetiltransferasas/genética; ARN Mensajero/genética; Factores de Transcripción/genética; Proteínas Adaptadoras Transductoras de Señales/metabolismo; Animales; Secuencia de Bases; Proteínas Portadoras/metabolismo; Mapeo Cromosómico; Córnea/metabolismo; Córnea/patología; Distrofias Hereditarias de la Córnea/metabolismo; Distrofias Hereditarias de la Córnea/patología; Modelos Animales de Enfermedad; Exones; Estudios de Asociación Genética; Prueba de Complementación Genética; Histona Acetiltransferasas/metabolismo; Humanos; Intrones; Ratones; ARN Mensajero/metabolismo; Eliminación de Secuencia; Factores de Transcripción/metabolismo

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / ARN Mensajero / Reordenamiento Génico / Proteínas Portadoras / Distrofias Hereditarias de la Córnea / Cromosomas de los Mamíferos / Proteínas Adaptadoras Transductoras de Señales / Histona Acetiltransferasas Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google