Abstract
High voltage-activated Cav2.3 R-type Ca2+ channels and low voltage-activated Cav3.2 T-type Ca2+ channels were reported to be involved in numerous physiological and pathophysiological processes. Many of these findings are based on studies in Cav2.3 and Cav3.2 deficient mice. Recently, it has been proposed that inbreeding of Cav2.3 and Cav3.2 deficient mice exhibits significant deviation from Mendelian inheritance and might be an indication for potential prenatal lethality in these lines. In our study, we analyzed 926 offspring from Cav3.2 breedings and 1142 offspring from Cav2.3 breedings. Our results demonstrate that breeding of Cav2.3 deficient mice shows typical Mendelian inheritance and that there is no indication of prenatal lethality. In contrast, Cav3.2 breeding exhibits a complex inheritance pattern. It might be speculated that the differences in inheritance, particularly for Cav2.3 breeding, are related to other factors, such as genetic specificities of the mutant lines, compensatory mechanisms and altered sperm activity.
Highlights
High voltage-activated Cav2.3 R-type Ca2+ channels and low voltage-activated Cav3.2 T-type Ca2+ channels were reported to be involved in numerous physiological and pathophysiological processes
For the C av3.2+/− × C av3.2+/− breeding scheme with 344 offspring from 58 litters, a deviation from Mendelian inheritance was detected with an increase of Cav3.2+/−, and a decrease of Cav3.2+/+ and Cav3.2−/− mice compared to the Mendelian distribution
Whether this phenomenon is related to prenatal lethality—as suggested by Alpdogan et al (2020)—cannot be specified here, as no scientific evidence is yet available to prove this hypothesis
Summary
High voltage-activated Cav2.3 R-type Ca2+ channels and low voltage-activated Cav3.2 T-type Ca2+ channels were reported to be involved in numerous physiological and pathophysiological processes. Many of these findings are based on studies in Cav2.3 and Cav3.2 deficient mice. In order to get more detailed insight into the physiological relevance of the various VGCCs, scientific groups around the world have inactivated the different C av-α1 subunits These studies have tremendously increased our understanding on the role of VGCCs and their involvement in the etiopathogenesis of animal and human d iseases[1,5,14]. Mouse lines lacking the C av2.3 or the C av3.2 VGCCs have first been generated and described 17–20 years ago and many physiological/pathophysiological implications of both channels were characterized in these models. Cav2.3 knockout mice, for example, exhibit a complex phenotype including, i.a., impaired pancreatic beta cell function and glucose tolerance[15,16,17], cardiac arrhythmia and altered autonomic r egulation[18,19,20], reduced seizure susceptibility[21,22,23,24,25,26,27], dysregulation in hippocampal theta genesis and altered theta architecture[28,29], impaired presynaptic long‐term potentiation (LTP)[30], distorted circadian rhythmicity and sleep[31,32], altered myelinogenesis[33], modified (neuropathic) pain p erception[34,35,36], enhanced fear[37] and altered auditory information p rocessing38,39. Cav2.3 VGCCs serve as key factors in regulating neuronal firing in the CNS, i.e., the tonic, intermediate and burst firing modes and modulate facultative neuronal oscillatory activity in specific neuronal ensembles and networks[40,41,42,43,44,45]
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