Lmx1a encodes a LIM homeodomain (LIM-hd) protein that is expressed in the roof plate along the neuraxis during CNS development. The Lmx1adr-J mutation replaces a conserved cysteine in the LIM1 domain of the protein with a tyrosine (Millonig et al. 2000).
Mice homozygous for Lmx1adr-Jare identifiable at birth by a thin filament extending from the end of the tail, which drops off within a few days, and a short or blunt tail. They may also have a head bleb. When fur develops, there may be a white belly spot. Lmx1adr-J/Lmx1adr-J mice are ataxic and hyperactive and have difficulty righting themselves, and they do not reproduce (Sweet and Wahlsten 1983). They also exhibit circling behavior, are deaf, and have inner ear and vertebral malformations (Manzanares et al. 2000).
Lmx1adr-J homozygotes exhibit defects of three classes of anatomic structures: the hindbrain roof plate, neural crest derived tissues, and the axial skeleton. Failure of roofplate development results in absence of dorsal interneurons of the spinal cord and of granule neurons of the cerebellar cortex and failure of the dorsal vertebral neural arches to form (Millonig et al. 2000). The cerebellum is smaller than normal, in some cases virtually absent, and exhibits disrupted foliation (Sweet and Wahlsten 1983; Sekiguchi et al. 1992). The cytoarchitectural organization of the neocortex, the hippocampus and the dentate gyrus is disrupted (Sekiguchi et al. 1992, 1993, 1994, 1996). Skeletal anomalies include abnormal neural crest derived cranial bones and improper fusion of cervical and thoracic vertebrae at the dorsal midline (Mananares et al. 2000). Deafness may be the consequence of "serious morphogenetic defects of the otic vesicle due to the dorsal neural tube abnormalities," perhaps augmented by "abnormal sensory and motor projections" in the region of rhombomeres 4-6 (Manzanares et al. 2000). Although they have no external or behavioral phenotype, 50% of heterozygotes exhibit histological pathology of the hippocampus qualitatively similar, but less extensive, than that of homozygotes (Patrylo et al. 1990).
