Reeler

The reeler mouse ( engl. to reel = sway, stagger ) is a spontaneously occurring mutation of the house mouse was first described in 1951. It is characterized by a typical swaying gait, tremor and ataxia ( general deficits in balance and motor coordination ) (Media: Reeler.ogg ).

There are different variants ( alleles ) of the reeler mutation in different mouse strains. Basically all reeler mice, however, an intact gene for the formation and secretion of the extracellular glycoprotein Reelin is missing. Reelin plays a special role in early embryonic and postnatal brain development. Therefore, the reeler mouse is studied as a model for case-sensitive brain development, especially in neurobiology.

A similar genetic defect in humans causes the disease lissencephaly, a disorder of neuronal migration, which leads to the degeneration of the child's brain. Among experts discussed often controversial, the reeler mouse is considered as a model for certain aspects of other neuronal disorders such as schizophrenia, epilepsy or Alzheimer 's disease.

The reeler brain

The brain of reeler mice differs significantly from the macroscopically and microscopically normal mice. The cerebellum is significantly reduced in size (approx. 30% ) and does not show the typical microscopic observation lamination into different cell layers. The cerebral cortex (Latin cortex) and the hippocampus are also greatly modified in their cellular architecture. While in the normal brain the cortex can be generally divided into six layers, it seemed at first as if this stratification was completely abolished in reeler mice.

However, it was shown that the cortical layering is not canceled completely in the reeler mouse, but that it is rather on the head. That is, nerve cells, which are normally in the deep layers of the cortex, can be found in the reeler mouse in the direction of brain surface and vice versa. This phenomenon is directly related to the function of the " reelin " protein during embryonic development. Although it is still argued about the exact mode in professional circles, is generally recognized that as a signaling molecule Reelin influence the migration of neurons during brain development. Therefore, the absence of Reelin in the brain of the reeler mouse leads to impaired neuronal migration.

Development of the reeler cortex

Neocortical neurons emerge from precursor cells of actively dividing zone - the so-called ventricular zone - which is located near the lateral ventricle of the brain. The first structure is formed, the so-called " Preplate ", a dense cell layer of Reelin -producing Cajal - Retzius cells and adjacent thereto " subplate " cells. Newly formed neurons from the ventricular zone migrate into the Preplate and split this into an upper and a lower layer. Each new generation of neurons formed by migrating their precursor layer until it reaches the upper part of the former Preplate. The layers on the surface are in the adult cortex are therefore created later than deeper layers. One speaks therefore of the layering of the cortex was developing an "inside first, outside last " mode.

In the reeler mouse, this mechanism of cortical development is disturbed. Newly formed neurons in reeler mutants are incapable in the " Preplate " immigrate and to split them and thus accumulate gradually below the first-formed Preplate, whereby the "inside first, outside last " mode of cortical layering is ultimately reversed.