An unstable targeted allele of the mouse Mitf gene with a high somatic and germline reversion rate.
Genetics
; 178(1): 259-72, 2008 Jan.
Article
en En
| MEDLINE
| ID: mdl-18202372
ABSTRACT
The mouse Mitf gene encodes a transcription factor that is regulated by serine phosphorylation and is critical for the development of melanin-containing pigment cells. To test the role of phosphorylation at a particular serine, S73 in exon 2 of Mitf, we used a standard targeting strategy in mouse embryonic stem cells to change the corresponding codon into one encoding an alanine. By chance, we generated an allele in which 85,222 bp of wild-type Mitf sequence are duplicated and inserted into an otherwise correctly targeted Mitf gene. Depending on the presence or absence of a neomycin resistance cassette, this genomic rearrangement leads to animals with a white coat with or without pigmented spots or a gray coat with obligatory white and black spots. Several independent, genetically stable germline revertants that lacked the duplicated wild-type sequence but retained the targeted codon were then derived. These animals were normally pigmented, indicating that the serine-to-alanine mutation is not deleterious to melanocyte development. The fact that mosaic coat reversions occur in all mice lacking the neo-cassette and that approximately 1% of these transmit a reverted allele to their offspring places this mutation among those with the highest spontaneous reversion rates in mammals.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Mutación de Línea Germinal
/
Alelos
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Factor de Transcripción Asociado a Microftalmía
Límite:
Animals
Idioma:
En
Año:
2008
Tipo del documento:
Article