Insertion of long interspersed element‐1 in the M itf gene is associated with altered neurobehavior of the black‐eyed white M itf mi‐bw mouse

Microphthalmia‐associated transcription factor ( M itf) is required for the differentiation of melanoblasts of the neural crest origin. The mouse homozygous for the black‐eyed white ( M itf mi‐bw ) allele is characterized by white‐coat color and deafness with black eye, due to the loss of melanoblasts during embryonic development. The M itf mi‐bw allele carries an insertion of long interspersed element‐1 ( L 1) in intron 3 of the M itf gene, which may cause the deficiency of melanocyte‐specific M itf‐ M . Here, we show that the L 1 insertion results in the generation of alternatively spliced M itf‐ M m RNA species, such as M itf‐ M m RNA lacking exon 3, exon 4 or both exons 3 and 4, each of which encodes M itf‐ M protein with an internal deletion. Transient expression assays showed the loss of or reduction in function of each aberrant M itf‐ M protein and the dominant negative effect of M itf‐ M lacking exon 4 that encodes an activation domain. Thus, the L 1 insertion may decrease the expression level of functional M itf‐ M . Importantly, M itf‐ M m RNA is expressed in the wild‐type mouse brain, with the highest expression level in the hypothalamus. Likewise, aberrant M itf‐ M m RNA s are expressed in the bw mouse brain. The bw mice show the altered neurobehavior under a stressful environment, suggesting the role of M itf‐ M in sensory perception.