Disease relevance of Cacna2d2

• The apneas of many torpid mammals can persist longer than estimated O2 stores allow [1].
• We conclude that the high metabolic efficiency and obesity of the glutamate-obese mouse are principally a consequence of its maintenance of a hypothermic torpid state for more than 50% of the time [2].

Psychiatry related information on Cacna2d2

• Mouse lemurs remained torpid between 1.7-8.9 h with a daily mean of 3.4 h, and their Tsk s fell to a minimum of 18.8 degrees C. Mean home ranges of mouse lemurs which remained normothermic were similar in the rainy and dry season [3].

High impact information on Cacna2d2

• Here we report that mice homozygous for targeted disruption of the Cacna2d2 gene exhibit growth retardation, reduced life span, ataxic gait with apoptosis of cerebellar granule cells followed by Purkinje cell depletion, enhanced susceptibility to seizures, and cardiac abnormalities [4].
• The underlying mutation was mapped to chromosome 9 (60.1 centimorgans) and identified as an allele of the Cacna2d2 gene encoding the alpha2delta-2 subunit of voltage-gated calcium channels [5].
• Cerebellar ataxia, seizures, premature death, and cardiac abnormalities in mice with targeted disruption of the Cacna2d2 gene [4].
• A mutation in Cacna2d2, the gene encoding the alpha 2 delta-2 voltage-dependent calcium channel accessory subunit, has been found to underlie the ducky phenotype [6].
• The mutation in alpha 2 delta-2 results in the introduction of a premature stop codon and predicts the expression of a truncated protein encoded by the first three exons of Cacna2d2, followed by 8 novel amino acids [6].

Biological context of Cacna2d2

• The ducky2J Mutation in Cacna2d2 Results in Reduced Spontaneous Purkinje Cell Activity and Altered Gene Expression [7].
• Surfactant from torpid animals is more active at 20 degrees C and less active at 37 degrees C than that of warm-active animals, which may represent a respiratory adaptation to low body temperatures of torpid dunnarts [8].
• MCP preferentially degrades oxidatively-damaged proteins and quantification of protein carbonyl content showed that the level of oxidatively-damaged protein in skeletal muscle decreased by > 75% during hibernation suggesting a continuing role for the MCP in the torpid state [9].
• The crystals are present in active and in torpid animals and during normal or induced spermatogenesis; their presence, therefore, does not seem to be dependent on the hormonal status of the hibernator [10].

Anatomical context of Cacna2d2

• We show that both mRNA and protein corresponding to this predicted transcript are expressed in du/du cerebellum and present in Purkinje cells [6].
• We observed a approximately 75-kDa band that was specifically increased in brush border membranes isolated from torpid squirrels compared with summer active squirrels [11].
• The sequence results were confirmed using anti-moesin antibodies that detected strong bands at approximately 75 kDa on Western blots of brush border membranes in torpid squirrels (Tb approximately 7 degreesC) and only faint signals in summer squirrels (Tb approximately 37 degrees C) or aroused hibernators (Tb approximately 37 degrees C) [11].
• These results provide evidence for the physiological induction of an ERM protein in intestinal epithelial cells of torpid hibernators and support the idea that hibernation involves differential expression of gene products that may facilitate viability of cells at low temperatures [11].

Associations of Cacna2d2 with chemical compounds

• Under most incubation conditions, glucose oxidation was significantly lower in tissues taken from torpid mice than in these tissues from normothermic mice, suggesting that adjustments in addition to changes in acid-base and substrate parameters may be necessary to account for metabolic modifications during daily torpor [12].
• This study sought experimental confirmation of passive O2 uptake in the pocket mouse Perognathus parvus, torpid at a body temperature of 10 degrees C, body mass 16.0 +/- 0.6 g (N = 9) [1].

Other interactions of Cacna2d2

• The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated alpha 2 delta-2 protein with abnormal function [6].
• The pituitary of female 'torpid' mice at the age of sexual maturity was deficient in prolactin cells [13].

Analytical, diagnostic and therapeutic context of Cacna2d2

• Five micrograms of phospholipid per centimeter squared surface area of whole lavage (from mice or from warm-active, 4-, or 8-h torpid dunnarts) were applied dropwise onto the sub-phase of a Wilhelmy-Langmuir balance at 20 degrees C and stabilized for 20 min [8].

References