Eyeless: Pitx3 mutant mouse line, Expression profiling of liver

ABSTRACT: A new mouse mutant arose spontaneously at the 5th inbred generation in a congenic C3H/He line. Since the mice suffered from anophthalmia or microphthalmia, we referred to this new mutant as eyeless (provisional gene symbol: eyl). The mutation follows an autosomal recessive pattern of inheritance and was mapped to chromosome 19 close to Pitx3; complementation tests confirmed that eyl is an allelic variant of aphakia (gene symbol: ak). Sequence analysis of the Pitx3 gene identified an insertion of a G in exon 4 (after cDNA position 416: 416insG). The altered open reading frame is predicted to result in a hybrid protein still containing the Pitx3 homeobox, but 121 new amino acids instead of the OAR domain at its C-terminal part. The new Pitx3eyl allele shares the ophthalmological and brain defects of the aphakia mouse including the loss of dopamine transporter 1 transcripts in the midbrain. Moreover, we observed in the mutants an increased extramedullary hematopoiesis in the spleen, and frequently also hepatosteatosis, combined with a reduced body weight. Fat mass, fat content and subcutaneous fat are significantly decreased in females, but not in males. Additionally, we observed a broad spectrum of behavioural changes in the homozygous mutants including reduced forelimb grip strength and increased nociception. In addition to these alterations being apparent in both sexes, we observed in female Pitx3eyl-/- mice increased anxiety, reduced locomotor activity, reduced object exploration and increased social contacts, but decreased anxiety and increased arousal in males. Most of these defects identified in the new Pitx3 mutation can also be observed in Parkinson patients. Therefore, the Pitx3eyl mutant is a valuable new model, because it is the first mutant mouse line carrying a point mutation within the coding region of the Pitx3 gene.

ORGANISM(S): Mus musculus

PROVIDER: GSE15336 | GEO | 2009/12/01

SECONDARY ACCESSION(S): PRJNA116567

REPOSITORIES: GEO