Non-Mendelian inheritance during inbreeding of Ca(v)3.2 and Ca(v)2.3 deficient mice

Ca(v)3.2 和 Ca(v)2.3 缺陷小鼠近亲繁殖过程中的非孟德尔遗传

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Abstract

The mating of 77 heterozygous pairs (Ca(v)3.2[+|-] x Ca(v)3.2[+|-]) revealed a significant deviation of genotype distribution from Mendelian inheritance in weaned pups. The mating of 14 pairs (Ca(v)3.2[-|-] female x Ca(v)3.2[+|-] male) and 8 pairs (Ca(v)3.2[+|-] female x Ca(v)3.2[-|-] male) confirmed the significant reduction of deficient homozygous Ca(v)3.2[-|-] pups, leading to the conclusion that prenatal lethality may occur, when one or both alleles, encoding the Ca(v)3.2T-type Ca(2+) channel, are missing. Also, the mating of 63 heterozygous pairs (Ca(v)2.3[+|-] x Ca(v)2.3[+|-]) 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 Ca(v)2.3[-|-] male mice lacking both alleles of the R-type Ca(2+) 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 Ca(2+) currents are higher expressed in some tissues than postnatally. It will be discussed that the function of voltage-gated Ca(2+) channels during prenatal development must be investigated in more detail, not least to understand devastative diseases like developmental epileptic encephalopathies (DEE).

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