Редактирование: ALS2

Alsin (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 6 protein) (Amyotrophic lateral sclerosis 2 protein) [ALS2CR6] [KIAA1563]

==Publications==

{{medline-entry
|title=Age-dependent deterioration of locomotion in Drosophila melanogaster deficient in the homologue of amyotrophic lateral sclerosis 2.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/24702731
|abstract=Recessive mutations in the amyotrophic lateral sclerosis 2 ([[ALS2]]) gene have been linked to juvenile-onset [[ALS2]]. Although one of the molecular functions of the [[ALS2]] protein is clearly the activation of Rab5, the mechanisms underlying the selective dysfunction and degeneration of motor neurons in vivo remain to be fully understood. Here, we focused on the [[ALS2]] homologue of Drosophila melanogaster, isolated two independent deletions, and systematically compared phenotypes of the mutants with those of animals in which Rab5 function in identified neurons was abrogated. In the d[[ALS2]] mutant flies, we found that the stereotypic axonal and dendritic morphologies of neurons shared some features with those in Rab5-deficient flies, but the d[[ALS2]] mutant phenotypes were much milder. We also found that the abrogation of Rab5 function in motor neurons strongly depressed the locomotion activity of adults, resembling the behavior of aged d[[ALS2]] mutants. Importantly, this age-dependent locomotion deficit of d[[ALS2]] mutants was restored to normal by expressing the d[[ALS2]] transgene in a wide range of tissues. This finding provided a platform where we could potentially identify particular cell types responsible for the phenotype by tissue-specific rescue experiments. We discuss our results and the future usage of the d[[ALS2]] mutant as a new ALS model. 
|mesh-terms=* Aging
* Animals
* Cell Line
* Drosophila Proteins
* Drosophila melanogaster
* Guanine Nucleotide Exchange Factors
* Heparin Lyase
* Humans
* Locomotion
* Motor Neurons
* Mutation
* Oxidative Stress
* Phenotype
* rab5 GTP-Binding Proteins

|full-text-url=https://sci-hub.do/10.1111/gtc.12146
}}
{{medline-entry
|title=Genetic background and gender effects on gross phenotypes in congenic lines of [[ALS2]]/alsin-deficient mice.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/20558214
|abstract=Loss-of-function mutations in human [[ALS2]] account for several juvenile recessive motor neuron diseases (MNDs). To understand the molecular basis underlying motor dysfunction in [[ALS2]]-linked MNDs, several lines of Als2(-/-) mice with a mixed genetic background were thus far generated, and their phenotypes were thoroughly characterized. However, several phenotypic discrepancies among different Als2-deficient lines became evident. To investigate whether genetic backgrounds are associated with such discrepancies, we here generated congenic lines of Als2(-/-) mice on two different genetic backgrounds; C57BL/6 (B6) and FVB/N (FVB), and investigated their gross phenotypes. Both B6 and FVB congenic lines were viable and fertile with no evidences for obvious abnormalities. There were no differences in growth curves between wild-type and Als2(-/-) mice on each genetic background. Remarkably, Als2(-/-) mice on a FVB, but not a B6, background exhibited a shorter life span than wild-type litters. Further, B6 female, but not male, Als2(-/-) mice showed a significantly lower spontaneous rearing activity than wild-type litters. These genetic background- and/or gender-specific findings suggest the presence of modifiers for life span and motor activities in Als2(-/-) mice. These congenic mice should provide a useful means to understand the molecular and genetic basis for variable expression of pathological phenotypes in MNDs.
|mesh-terms=* Amyotrophic Lateral Sclerosis
* Analysis of Variance
* Animals
* Body Weight
* Disease Models, Animal
* Female
* Guanine Nucleotide Exchange Factors
* Longevity
* Male
* Mice
* Mice, Congenic
* Mice, Knockout
* Motor Activity
* Phenotype
* Psychomotor Performance
* Sex Characteristics
* Survival Analysis

|full-text-url=https://sci-hub.do/10.1016/j.neures.2010.06.004
}}