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

Figure 1

Real and theoretical average number of offspring from different Ca_v3.2 breeding schemes. (A_I–C_I) Breeding results for both sexes using a Ca_v3.2^+/− × Ca_v3.2^+/−, Ca_v3.2^+/− × Ca_v3.2^+/+ and Ca_v3.2^+/− × Ca_v3.2^−/− breeding scheme. In addition, these data were analyzed separately for male offspring (A_II–C_II) and female offspring (A_III–C_III). Plain bars indicate real average offspring number, patterned bars indicate the theoretical average offspring number based on the Mendelian inheritance.

Figure 2

Real and theoretical average number of offspring from different Ca_v2.3 breeding schemes. (A_I–C_I) Breeding results for both sexes using a Ca_v2.3^+/− × Ca_v2.3^+/−, Ca_v2.3^+/− × Ca_v2.3^+/+ and Ca_v2.3^+/− × Ca_v2.3^−/− breeding scheme. In addition, these data were analyzed separately for male offspring (A_II–C_II) and female offspring (A_III–C_III). Plain bars indicate real average offspring number, patterned bars indicate the theoretical average offspring number based on the Mendelian inheritance.