Factors in the Genetic Background Suppress theEngrailed-1Cerebellar Phenotype

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Abstract
The mouse homeodomain protein, Engrailed-1, is generally viewed as an essential player in the early establishment and maintenance of the midbrain/hindbrain region that gives rise to the cerebellum and midbrain. In keeping with this, engineered null mutations at this locus have been reported to lead to perinatal lethality accompanied by near-total absence of cerebellar and caudal midbrain structures. We report here that these cerebellar phenotypes are nearly completely suppressed on a C57BL/6J genetic background. All cell types are present and arranged properly in both the cortex and the deep nuclei, and cell counts reveal no significant absence of cerebellar Purkinje cells. Folial patterns are nearly normal, although an apparent fusion of lobules IV and V is consistently noted. Significantly, no change in theEngrailed-2mutant phenotype occurs after a similar background switch, and whole-mountin situhybridization reveals identicalEn2expression patterns in wild-type C57BL/6J and 129/Sv mice. One likely mechanism for theEn1-/-phenotype suppression is a temporal and/or spatial change in the pattern of Engrailed-2 expression apparent only in the absence of Engrailed-1. In support of this, C57BL/6—En1-/-embryos that are alsoEn2+/-lack a cerebellum and caudal midbrain: a phenotype identical to 129/Sv—En1-/-mice.