MouseDach2 mutants do not exhibit gross defects in eye development or brain function

Abstract

Drosophila dachshund is a critical regulator of eye, brain, and limb formation. Vertebrate homologs, Dach1 and Dach2, are expressed in the developing retina, brain, and limbs, suggesting functional conservation of the dachshund/Dach gene family. Dach1 mutants die postnatally, but exhibit grossly normal development. Here we report the generation of Dach2 mutant mice. Although deletion of Dach2 exon 1 results in abrogation of RNA expression, Dach2 mutants are viable and fertile. Histochemical analysis reveals grossly normal Dach2 mutant eye development. In addition, a battery of neurological assays failed to yield significant differences in behavior between Dach2 mutants and controls. We discuss these findings in the light of published observations of DACH2 mutations in the human population. Finally, to test the functional conservation hypothesis, we generated Dach2; Dach1 double mutant mice. Dach double mutants die after birth, similar to Dach1 homozygotes. However, unlike Drosophila dachshund mutants that lack eyes and exhibit leg truncations, the eyes and limbs of Dach double mutants are present, suggesting differences between Dach and dachshund gene function during embryonic eye and limb formation.

Dach2-Hdac9 signaling regulates reinnervation of muscle endplates

“…−/− and Hdac9 −/− mice were previously described (Zhang et al, 2002;Méjat et al, 2005;Davis et al, 2006). Dach2 ;CAGG-CreER) were described previously (Knapp et al, 2006).…”

The Eyes Absent Family of Phosphotyrosine Phosphatases: Properties and Roles in Developmental Regulation of Transcription

“…The Dach family, first defined by Drosophila Dac and represented by two paralogs in vertebrates, Dach1 and Dach2, comprises nuclear proteins characterized by two conserved domains, the DachBox-N/DD1 and the DachBox-C/DD2 (Figure 2b) (6,(44)(45)(46). Both DD1 and DD2 show similarity to motifs found in the Ski/Sno proto-oncogenes, raising the possibility that like Ski/Sno, Dach may function as a transcriptional repressor (44,46).…”

“…In vertebrates, Dach1 is expressed in the developing eye, but the expression pattern of Dach2 is uncharacterized (44,46). However, neither single nor compound Dach1 and Dach2 homozygous mutant mice exhibit eye abnormalities (45,51), suggesting Dach1 and Dach2 may be dispensable or play a very minor role in eye development in vertebrates.…”

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade

“…In addition, siRNA-mediated Dach2 knockdown is not complete, and residual Dach2 expression may be sufficient to maintain low levels of Mgn gene expression. Recently, a Dach2 knockout mouse was generated and found to be viable with no gross defects in eye or brain development (36). Although skeletal muscle was not specifically examined, limbs were reported to appear normal.…”