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Breeding of Ca_v2.3 deficient mice reveals Mendelian inheritance in contrast to complex inheritance in Ca_v3.2 null mutant breeding.

ABSTRACT: High voltage-activated Ca_v2.3 R-type Ca²⁺ channels and low voltage-activated Ca_v3.2 T-type Ca²⁺ channels were reported to be involved in numerous physiological and pathophysiological processes. Many of these findings are based on studies in Ca_v2.3 and Ca_v3.2 deficient mice. Recently, it has been proposed that inbreeding of Ca_v2.3 and Ca_v3.2 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 Ca_v3.2 breedings and 1142 offspring from Ca_v2.3 breedings. Our results demonstrate that breeding of Ca_v2.3 deficient mice shows typical Mendelian inheritance and that there is no indication of prenatal lethality. In contrast, Ca_v3.2 breeding exhibits a complex inheritance pattern. It might be speculated that the differences in inheritance, particularly for Ca_v2.3 breeding, are related to other factors, such as genetic specificities of the mutant lines, compensatory mechanisms and altered sperm activity.

SUBMITTER: Papazoglou A

PROVIDER: S-EPMC8263769 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Breeding of Cav2.3 deficient mice reveals Mendelian inheritance in contrast to complex inheritance in Cav3.2 null mutant breeding.

Papazoglou Anna A Henseler Christina C Broich Karl K Daubner Johanna J Weiergräber Marco M

Scientific reports 20210707 1

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 inherita ...[more]

PMID: 34234221

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Project description:Characterizing the distinct functions of the T-type ion channel subunits Cav3.1, 3.2 or 3.3 has proven difficult due to their highly conserved amino-acid sequences and the lack of pharmacological blockers specific for each subunit. To precisely determine the expression pattern of the Cav3.2 channel in the nervous system we generated two knock-in mouse strains that express EGFP or Cre recombinase under the control of the Cav3.2 gene promoter. We show that in the brains of these animals, the Cav3.2 channel is predominantly expressed in the dentate gyrus of the hippocampus. In the peripheral nervous system, the activation of the promoter starts at E9.5 in neural crest cells that will give rise to dorsal root ganglia (DRG) neurons, but not sympathetic neurons. As development progresses the number of DRG cells expressing the Cav3.2 channel reaches around 7% of the DRG at E16.5, and remains constant until E18.5. Characterization of sensory neuron subpopulations at E18.5 showed that EGFP+ cells are a heterogeneous population consisting mainly of TrkB+ and TrkC+ cells, while only a small percentage of DRG cells were TrkA+. Genetic tracing of the sensory nerve end-organ innervation of the skin showed that the activity of the Cav3.2 channel promoter in sensory progenitors marks many mechanoreceptor and nociceptor endings, but spares slowly adapting mechanoreceptors with endings associated with Merkel cells. Our genetic analysis reveals for the first time that progenitors that express the Cav3.2 T-type calcium channel, defines a sensory specific lineage that populates a large proportion of the DRG. Using our Cav3.2-Cre mice together with AAV viruses containing a conditional fluorescent reporter (tdTomato) we could also show that Cre expression is largely restricted to two functionally distinct sensory neuron types in the adult ganglia. Cav3.2 positive neurons innervating the skin were found to only form lanceolate endings on hair follicles and are probably identical to D-hair receptors. A second population of nociceptive sensory neurons expressing the Cav3.2 gene was found to be positive for the calcitonin-gene related peptide but these neurons are deep tissue nociceptors that do not innervate the skin.

Dataset Information

Breeding of Ca_v2.3 deficient mice reveals Mendelian inheritance in contrast to complex inheritance in Ca_v3.2 null mutant breeding.

Publications

Breeding of Ca<sub>v</sub>2.3 deficient mice reveals Mendelian inheritance in contrast to complex inheritance in Ca<sub>v</sub>3.2 null mutant breeding.

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