Airway responsiveness is counted from inside the 40 Good/J, 4step one C3H/HeJ, 40 (C3H/HeJ ? A/J) F

₁, 40 (A/J ? C3H/HeJ) F₁, 104 (A/J ? C3H/HeJ) F_dos intercross, and 369 [(A/J ? C3H/HeJ)F₁? C3H/HeJ] backcross mice; the values forR_L, expressed as a percentage of baseline for the 330 and 1,000 ?g/kg doses, are shown in Table 1 along with the log ED₁₅₀R_Lvalues. A scatterplot ofR_L values for the 330 ?g/kg dose (expressed as a percentage of baseline) from individual parental, F₁, F₂, and backcross mice is presented in 1 and as the log ED₁₅₀R_Lvalues in 2. Analysis of the distribution of airway responsiveness phenotypes in the A/J and C3H/HeJ parental strains confirmed the original observations that A/J mice are more responsive to challenge with cholinergic bronchoconstrictors than C3H/HeJ mice (8, 11).

Fig

F1-153 n = 365. R_L, pulmonary resistance; log ED₁₅₀R_L, log-transformed dose required for a 1.50-fold increase inR_L; ACF₁, A/J female mated with C3H/HeJ male F₁ hybrid strain; backcross, [(A/J ? C3H/HeJ)F₁ ? C3H/HeJ] mice.

1.Scatterplot of pulmonary resistance (R _{ACF1, A/J female mated with CeH/HeJ male F1 hybrid; CAF1, C3H/HeJ female mated with A/J male F1 hybrid; backcross, [(A/J ? C3H/HeJ)F1? C3H/HeJ]; n, no. of mice. * Significantly different from C3H/HeJ mice,P < 0.05.}

2.Scatterplot of R_Lvalues for log-transformed dose required for 1.50-fold increase inR_L (log ED₁₅₀R_L) for parental and hybrid mice. Distribution of airway responsiveness phenotypes and therefore genetically informative progeny in F₂ intercross group is narrower than range of responses to 330 ?g/kg dose (expressed as a percentage of baseline). n, No. of mice.

Analysis of the distribution of individual animals demonstrates that the mode of inheritance does not follow a simple Mendelian or complex genetic pattern. TheR_L values for the 330 ?g/kg dose, expressed as a percentage of baseline, are presented in 1. Analysis of F₁ mice derived from reciprocal crosses [A/J females mated with C3H/HeJ males (ACF₁) and C3H/HeJ females with A/J males (CAF₁)] revealed significant differences in airway responsiveness. Both F₁ hybrids had a phenotype that was intermediate between the A/J and C3H/HeJ strains but was skewed more toward the A/J strain (Table 1). However, significantly greater responses were observed in the ACF₁ hybrid strain than in the CAF₁ strain (P < 0.0047; Table 1, 1). Airway responses were broadly distributed to encompass the range of values observed in the C3H/HeJ, F₁, and A/J groups ( 1) in F₂ mice derived from ACF₁ mice. A similar analysis of the log ED₁₅₀R_Lvalues for the parental and hybrid crosses revealed a narrower distribution of airway responses ( 2) than that in response to 330 ?g/kg of methacholine alone. Airway responsiveness in F₂ mice, ascertained with theR_L response to 330 or 1,000 ?g/kg of methacholine or log ED₁₅₀R_Lvalues, was not normally distributed (P < 0.0001 by Shapiro-WilkW-test for normality). Analysis of airway responses for the 330 ?g/kg dose in the F₂ intercross and CAF₁ mice indicated that 48% of the total variance in the intercross was genetic best places to live in Albuquerque for singles. The CAF₁ group was used to calculate the genetic component of the variance because the variability in airway responses in this F₁ group was significantly less compared with that in the ACF₁ cross.

Because airway hyperresponsiveness appeared to be intermediate in the ACF₁ mice but skewed toward the A/J phenotype, they were backcrossed to the hyporesponsive C3H/HeJ parental strain [(A/J ? C3H/HeJ) F₁ ? C3H/HeJ]. Airway responsiveness in 369 backcross progeny ( 1) was not normally distributed (P < 0.0001), a finding similar to that for the F₂ progeny (3).

L) values (indicated just like the a percentage off standard) out of personal parental and hybrid rats

3.Estimated distribution of methacholine response and normal quantile plot of backcross (A) and F₂ intercross (B) mice studied in terms ofR_L values for 330 ?g/kg dose. n, No. of mice. Neither F₂ intercross progeny nor backcross progeny were normally distributed.