Non-Mendelian inheritance during inbreeding of Cav3.2 and Cav2.3 deficient mice

Serdar Alpdogan,Renate Clemens,Felix Neumaier,Toni Schneider,Jürgen Hescheler

doi:10.1038/s41598-020-72912-9

Serdar Alpdogan, Renate Clemens + Show 3 more

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https://doi.org/10.1038/s41598-020-72912-9

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Journal: Scientific Reports	Publication Date: Oct 2, 2020
Citations: 5	License type: open-access

Affiliation: University of Cologne

Abstract

The mating of 77 heterozygous pairs (Cav3.2[+|−] x Cav3.2[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups. The mating of 14 pairs (Cav3.2[−|−] female x Cav3.2[+|−] male) and 8 pairs (Cav3.2[+|−] female x Cav3.2[−|−] male) confirmed the significant reduction of deficient homozygous Cav3.2[−|−] pups, leading to the conclusion that prenatal lethality may occur, when one or both alleles, encoding the Cav3.2T-type Ca2+ channel, are missing. Also, the mating of 63 heterozygous pairs (Cav2.3[+|−] x Cav2.3[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups, but only for heterozygous male mice, leading to the conclusion that compensation may only occur for Cav2.3[−|−] male mice lacking both alleles of the R-type Ca2+ channel. During the mating of heterozygous parents, the number of female mice within the weaned population does not deviate from the expected Mendelian inheritance. During prenatal development, both, T- and R-type Ca2+ currents are higher expressed in some tissues than postnatally. It will be discussed that the function of voltage-gated Ca2+ channels during prenatal development must be investigated in more detail, not least to understand devastative diseases like developmental epileptic encephalopathies (DEE).

Highlights

The mating of 77 heterozygous pairs (Cav3.2[+|−] x Cav3.2[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups
Voltage-gated Ca2+ channels (VGCCs) are a key mediator of Ca2+ entry from the extracellular space and enable Ca2+ signaling in a dual manner, electrogenically, via C a2+-induced changes in membrane potential, and biochemically, through the activation of C a2+ dependent enzymes and other proteins affecting cellular r egulation[3]
Ten mammalian genes are known to encode different ion conducting Cavα[1] subunits of these VGCCs, which have been subdivided into 7 high- and 3 low-voltage activated C a2+ channels

Summary

Introduction

The mating of 77 heterozygous pairs (Cav3.2[+|−] x Cav3.2[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups. The mating of 63 heterozygous pairs (Cav2.3[+|−] x Cav2.3[+|−]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups, but only for heterozygous male mice, leading to the conclusion that compensation may only occur for Cav2.3[−|−] male mice lacking both alleles of the R-type Ca2+ channel. Ten mammalian genes are known to encode different ion conducting Cavα[1] subunits of these VGCCs, which have been subdivided into 7 high- and 3 low-voltage activated C a2+ channels (for details,[4]). In vivo, they are assembled with additional auxiliary s ubunits[5], for which the complete setup of components is only partially known. During the breeding of these mice the number of weaned pups did not correspond the expected ratios for a Mendelian inheritance, pointing to a possible prenatal lethality

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