Reeler mouse

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Reeler mouse (Christian Cremer video)

The Reeler mouse ( English to reel , 'sway, tumble' ) is a spontaneously occurring mutation of the house mouse and was first described in 1951. It is characterized by a typically unsteady gait, tremor and ataxia (general deficits in balance and motor coordination) ( medium: Reeler.ogv ).

There are different variants ( alleles ) of the Reeler mutation in different mouse strains. Basically, all Reeler mice lack an intact gene for the formation or secretion of the extracellular glycoprotein Reelin . Reelin plays a special role in the early embryonic and postnatal development of the brain. Therefore, the Reeler mouse is studied primarily in neurobiology as a model for cerebral and cerebellar development.

A similar genetic defect in humans causes lissencephaly , a disorder of neuronal migration that leads to degeneration of the child's brain. Often debated among experts, the Reeler mouse is also considered a model for certain aspects of other neuronal diseases such as schizophrenia , epilepsy or Alzheimer's disease .

The reeler brain

Normal and Reeler brains

The brain of Reeler mice differs macroscopically and microscopically significantly from that of normal mice. The cerebellum is significantly reduced in size (approx. −30%) and, when viewed microscopically, does not show the typical lamination into different cell layers. The cerebral cortex ( Latin cortex) and the hippocampus are also heavily modified in their cellular architecture. While the cortex can usually be divided into six layers in the normal brain, it initially seemed as if this layering was completely eliminated in Reeler mice.

However, it has been shown that the cortical layering in the Reeler mouse is by no means completely canceled, but rather that it is upside down. I.e. Nerve cells, which are normally located in the deep layers of the cortex, are found in the Reeler mouse further towards the brain surface and vice versa. This phenomenon is directly related to the function of the “Reelin” protein during embryonic development. Although the exact mode is still debated among experts, it is generally accepted that reelin, as a signaling molecule, influences the migration of neurons during the development of the brain. The absence of Reelin in the brain of the Reeler mouse therefore leads to impaired neuronal migration.

Development of the Reeler Cortex

Neocortical neurons arise from precursor cells of a dividing zone - the so-called ventricular zone - which is located near the lateral cerebral ventricles . The first structure that is formed is the so-called "Preplate", a dense cell layer made of Reelin-producing Cajal-Retzius cells and adjacent "subplate" cells. Newly formed neurons from the ventricular zone migrate into the prepplate and split it into an upper and a lower layer. Each new generation of neurons formed travels through its precursor layer until it reaches the top of the previous prepplate. The layers that are more superficial in the adult cortex are therefore created later than the deeper layers. It is therefore said that the stratification of the cortex develops in an "inside first, outside last" mode.

This mechanism of cortical development is disturbed in the Reeler mouse. Newly formed neurons in Reeler mutants are unable to migrate into the “preplate” and split it and therefore collect step by step below the preplate formed first, whereby the “inside first, outside last” mode of the cortical layering is ultimately reversed.

Web links

  • Goffinet, AM: DENE Gofinet. Université catholique de Louvain, accessed November 19, 2008 .

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  1. ^ Falconer, DS: Two new mutants 'Trembler' and 'Reeler', with neurological actions in the house mouse . In: Journal of Genetics . No. 50 , 1951, pp. 192-201 (English).
  2. ↑ Hamburgh, M .: Observations on the neuropathology of "Reeler", a neurological mutation in mice . In: Experientia . No. 16 , 1960, pp. 460-461 (English).
  3. ^ Goffinet, AM: An early development defect in the cerebral cortex of the Reeler mouse. A morphological study leading to a hypothesis concerning the action of the mutant gene . In: Anatomy and Embryology 157 . 1979, ISSN  0340-2061 , p. 205-216 , doi : 10.1007 / BF00305160 (English).
  4. ^ D'Arcangelo, G .: The Reeler mouse: anatomy of a mutant . In: International review of neurobiology . tape 71 , 2005, p. 383-417 (English).
  5. ↑ Lambert de Rouvroit, C., Goffinet, AM: The reeler mouse as a model of brain development . In: Advances in Anatomy, Embryology and Cell Biology . No. 150 , 1998, pp. 1-106 (English).
  6. ^ D'Arcangelo, G .: Reelin mouse mutants as models of cortical development disorders . In: Epilepsy & behavior . February 2006, p. 81-90 (English).
  7. ↑ Fatemi, SH: Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly . In: Molecular psychiatry . March 2001, p. 129-133 (English).
  8. ↑ Patrylo, P., Browning R., Cranick, S .: Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity . In: Department of Physiology, Southern Illinois University School of Medicine (Ed.): Epilepsia . tape 47 , no. 2 , February 2006, ISSN  0013-9580 , p. 257-266 (English).
  9. ↑ Grilli, M., Toninelli, G., Uberti D., Spano, P., Memo, M .: Alzheimer's disease linking neurodegeneration with neurodevelopment . In: Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Brescia, Italy (Ed.): Functional neurology . tape 18 , no. 3 , 2003, ISSN  0393-5264 , p. 145-148 (English).
  10. ↑ Hamburgh, M .: ANALYSIS OF THE POSTNATAL DEVELOPMENTAL EFFECTS OF "REELER," A NEUROLOGICAL MUTATION IN MICE. A STUDY IN DEVELOPMENTAL GENETICS. In: Developmental biology . tape October 19 , 1963, ISSN  0012-1606 , p. 165-185 (English).
  11. ↑ Caviness VS Jr .: neocortical histogenesis in normal and reeler mice: a developmental study based upon [3H] thymidine autoradiography. In: Brain research . 1982, p. 293-302 (English).