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

Abstract

AbstractThe 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).