Generation and mutational analysis of a transgenic murine model of the human MAF mutation.
Am J Med Genet A
; 191(7): 1878-1888, 2023 07.
Article
en En
| MEDLINE
| ID: mdl-37186330
ABSTRACT
Aymé-Gripp syndrome is an autosomal dominant multisystem disorder. The major clinical features of this syndrome include congenital cataracts, sensorineural hearing loss, intellectual disability, and a distinctive flat facial appearance. MAF has been identified as a causative gene of the syndrome, and heterozygous variants owing to impairment in glycogen synthase kinase 3 (GSK3)-mediated MAF phosphorylation shows related disorders. However, the underlying mechanisms of these types of disorders in affected individuals remain poorly understood. To explore the underlying mechanisms and discover new phenotypes, a murine model with a Maf mutation on a GSK3 phosphorylation motif, p.Thr58Ile, was generated using CRISPR-Cas9 gene editing. This is a homologous mutation to that in human patients. Our murine model exhibited similar phenotypes to those in humans, such as lens abnormalities, short stature, growth retardation, and abnormal skull morphology. The murine model showed decreased brain volume and malocclusion. Considering the sequencing and genotyping data, our models were successfully generated for the first time (to the best of our knowledge). Therefore, this study offers new and unique functional insights into human and murine MAF and novel clinical values of MAF pathogenic variants associated with changes in the functions of several organs based on a viable murine model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Catarata
/
Pérdida Auditiva Sensorineural
/
Discapacidad Intelectual
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Am J Med Genet A
Asunto de la revista:
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Japón