Scrambler mouse
Encyclopedia
Scrambler is a spontaneous mouse mutant
lacking a functional DAB1
gene, resulting in a phenotype
resembling that seen in the reeler
mouse. The strain was first described by Sweet et al in 1996.
scrambler mutation on chromosome 4 causes a deficiency of DAB1
, encoding disabled-1, a protein involved in the signaling of the Reelin
protein, lacking in the reeler
mutant, Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus
, and neocortex
. Purkinje cell
and granule cell
degeneration results in ataxia
. Despite normal Reln mRNA levels, Dba1-scm mutants have defective reelin signaling, indicating that disabled-1 acts downstream of reelin. Cell ectopias are identical with targeted disruption of Dba1.
). In their home-cage, they often reel and fall, especially when attempting to rear up against the walls. Nevertheless, the mutants are fertile, and so can be reproduced from one generation to the next. Relative to non-ataxic controls of the same background strain, Dab1-scm mutants are impaired in the Rotarod Performance test
of motor coordination as well as a grid-climbing test. When picked up by the tail, they show a pathological reflex, limb-clasping, characterized by holding together fore- or hind-limbs, or all four together in a bat-like posture.
Mutant
In biology and especially genetics, a mutant is an individual, organism, or new genetic character, arising or resulting from an instance of mutation, which is a base-pair sequence change within the DNA of a gene or chromosome of an organism resulting in the creation of a new character or trait not...
lacking a functional DAB1
DAB1
The Disabled-1 gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway...
gene, resulting in a phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
resembling that seen in the reeler
Reeler
A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by profound hypoplasia of the mouse's cerebellum, in which the normal cerebellar folia are missing. The mutation is autosomal and recessive....
mouse. The strain was first described by Sweet et al in 1996.
Neuroanatomical abnormalities
The spontaneous autosomal recessiveRecessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
scrambler mutation on chromosome 4 causes a deficiency of DAB1
DAB1
The Disabled-1 gene encodes a key regulator of Reelin signaling. Reelin is a large glycoprotein secreted by neurons of the developing brain, particularly Cajal-Retzius cells. DAB1 functions downstream of Reln in a signaling pathway...
, encoding disabled-1, a protein involved in the signaling of the Reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
protein, lacking in the reeler
Reeler
A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by profound hypoplasia of the mouse's cerebellum, in which the normal cerebellar folia are missing. The mutation is autosomal and recessive....
mutant, Dba1-scm homozygous mutants possess a reeler-like phenotype with respect to cell malpositioning in cerebellar cortex, hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
, and neocortex
Neocortex
The neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
. Purkinje cell
Purkinje cell
For the cells of the electrical conduction system of the heart, see Purkinje fibersPurkinje cells, or Purkinje neurons , are a class of GABAergic neurons located in the cerebellar cortex...
and granule cell
Granule cell
In neuroscience, granule cells refer to tiny neurons that are around 10 micrometres in diameter. Granule cells are found within the granular layer of the cerebellum , the dentate gyrus of the...
degeneration results in ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
. Despite normal Reln mRNA levels, Dba1-scm mutants have defective reelin signaling, indicating that disabled-1 acts downstream of reelin. Cell ectopias are identical with targeted disruption of Dba1.
Behavioral abnormalities
Dab1-scm mutants have a wide-spread gait obvious to the naked eye (ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
). In their home-cage, they often reel and fall, especially when attempting to rear up against the walls. Nevertheless, the mutants are fertile, and so can be reproduced from one generation to the next. Relative to non-ataxic controls of the same background strain, Dab1-scm mutants are impaired in the Rotarod Performance test
Rotarod Performance test
The Rotarod Performance test is a performance test based on a rotating rod with forced motor activity being applied , usually by a rodent. The Rotarod Performance test measures parameters such as riding time or endurance...
of motor coordination as well as a grid-climbing test. When picked up by the tail, they show a pathological reflex, limb-clasping, characterized by holding together fore- or hind-limbs, or all four together in a bat-like posture.