Joubert syndrome (JS) is a neurodevelopmental disorder that is characterized by abnormal motor coordination, muscle tone, and problems in regulating breathing pattern and eye movements. A proportion of JS patients are affected in a number of other systems as well including the retina and kidney. Though four genes have been identified to be involved in JS, still very little is known about the mechanisms of this disease. The pathology in these patients suggest that the syndrome is due to impaired functioning of multiple systems in the midbrain/hindbrain and the wiring of axon tracts, in particular, the corticospinal tract (CST) as it crosses the midline in the brainstem. In preliminary studies, the laboratory has generated a knockout mouse of the Ahi1 gene, mutations of which has been shown to cause JS in humans. The goal of this study is to show that this mouse model is a model for JS in the following ways: testing Ahi1 mutant mice for behavioral defects associated with Joubert syndrome;characterizing the anatomical defects that may underlie these behaviors with standard histological and immunochemical techniques;and determining whether axons cross normally in the brainstem of Ahi1 knockout mice by introducing the EphA4:LacZ-PLAP allele (which will label the CST) into the Ahi1 knockout mouse background. This study will potentially provide the first genetic mouse model for JS. An understanding of the function of the Ahi1 gene in the mouse may significantly contribute to our knowledge of development of the midbrain-hindbrain and of brain wiring
| Louie, Carrie M; Caridi, Gianluca; Lopes, Vanda S et al. (2010) AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis. Nat Genet 42:175-80 |
