Mice homozygous for the reeler (Relnrl) mutation exhibit an ataxic gait, dystonic posture and. Neuronal layer formation fails in laminated brain regions during development, and there are reduced numbers of granule and Purkinje cells. T-cell and macrophage function are suppressed in homozygous mutants. Mutant reeler mice may serve as a murine model for general lissencephalic disorders that affect humans. Additionally, mice heterozygous for the Relnrl mutation may be useful in studies of dopamine-related pathophysiological disorders such as schizophrenia.Read More +
Mice homozygous for the reeler (Relnrl) mutation exhibit an ataxic gait, dystonic posture and tremors starting around 2 weeks of age. These mutants are incapable of maintaining their hindquarters upright and often fall over during locomotor activity. Moreover, viability and fertility are greatly reduced, especially when the gene is carried on an inbred genetic background. Heterozygotes are visually indistinguishable from wildtype controls. Neuropathies characteristic of Relnrl/Relnrl mutants include a failure of neuronal layer formation in laminated brain regions during development. Neuronal positioning is abnormal within cerebellar, cerebral and hippocampal cortices. The behavioral phenotype is primarily attributed to the severe hypoplasia of the cerebellum, which lacks foliation. Here, there are reduced numbers of granule and Purkinje cells and these cells are aberrantly dispersed among the layers. In the Reln-deficient neocortex, neurons normally destined to migrate past the subplate remain confined to deeper nuclei, thus ablating normal cortical layer formation. Similarly, pyramidal and granule cells of the developing hippocampus are scattered throughout the hippocampal tracts causing gross disorganization. RELN is required for normal spinal cord formation since migration of sympathetic preganglionic neurons in the intermediolateral column becomes disrupted in developing Relnrl/Relnrl mice. While somatic motor neurons and cholinergic interneurons are positioned normally in the Relnrl/Relnrl spinal cord, parasympathetic and sympathetic preganglionic neurons migrate medially past their normal destinations, indicating that RELN may act in a cell-specific manner. Neurons are also found abnormally positioned in the facial nucleus, inferior olivary complex, and mesencephalic trigeminal nucleus of affected reeler mutants. A RELN deficiency additionally results in an alteration in the structure and function of retinal synaptic circuitry. There is a reduction in the number of rod bipolar cells and physiologic responsiveness is compromised. Specifically, electroretinography analysis demonstrated a reduction in rod b-wave amplitudes. RELN may also play a role in the development of immune function since T-cell and macrophage function are suppressed in Relnrl/Relnrl mutants. Taken together, the data suggest that RELN functions in the extracellular matrix as a patterning signal for postmitotic neuronal migration along radial glial cell pathways. It may alternatively function to modulate neuron-neuron adhesivity and/or stability. Severe defects in neuronal cell migration underlie general lissencephalic disorders that affect humans. Therefore, the reeler mice may serve as a murine model for such neuronal ectopia disorders. Additionally, mice heterozygous for the Relnrl mutation are currently being pursued as a model for dopamine-related pathophysiological disorders such as schizophrenia. These Relnrl/+ mice exhibit a reduction in 1) the number of tryrosine hydroxylase-immunoreactive cell bodies, 2) tyrosine hydroxylase and dopamine transporter immunoreactivity, 3) tyrosine hydroxylase and D2 dopamine receptor mRNA levels in the mesolimbic dopamine system, and 4) oxytocin receptors in the piriform cortex, neocortex, retrosplenial cortex and certain regions of the hippocampus (reviewed by Rice and Curran, 2001, D'Arcangelo and Curran, 1998, and Hatten, 1999; Falconer, 1951; Soriano et al., 1997; Hunter-Schaedle, 1997; Caviness and Rakic, 1978; Caviness, 1982; Caviness et al., 1972; Rice et al., 2001; Yip et al., 2000; Phelps et al., 2002; Ballmaier et al., 2002; Liu et al., 2005).
The reeler mutation was reported by Falconer in 1951 as a spontaneous mutation in a mildly inbred stock. It is currently maintained on a B6C3FeF1 background by a backcross-Intercross mating system.
|Allele Synonym(s)||rl; rl-; rlJ; rlnrl|
|Gene Symbol and Name||Reln, reelin|
|Strain of Origin||"snowy-bellied" stock or unspecified inbred strain|
|General Note||Early studies were summarized and critically reviewed by Goffinet (J:12281).|
|Molecular Note||This allele comprises an apprxomately 126.7 kb deletion that has a breakpoint in an intron of reelin and removes coding sequence downstream of cDNA nucleotide 3619. No reelin mRNA is detected in homozygotes.|
|Gene Symbol and Name||a, nonagouti|
|Strain of Origin||old mutant of the mouse fancy|
|General Note||Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039|
|Molecular Note||Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.|
At The Jackson Laboratory, we use the combination of breeding scheme and phenotype to maintain our B6C3Fe a/a Relnrl/J colony.
1) Relnrl/Relnrl x B6C3FeF1/J a/a to generate obligate heterozygotes (Relnrl/+).
2) Relnrl/+ x Relnrl/+ to generate homozygotes, which are identified based on their phenotype: ataxic gait, dystonic posture and tremors.
When using the reeler mouse strain in a publication, please cite the originating article(s) and include JAX stock #000235 in your Materials and Methods section.
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