Figure 2

Postnatal growth retardation in mice carrying Cdkn1c transgene. A) Post natal growth curves of males from one to eight weeks for lines 5D3 (one copy, n = 2), 5A4 (two copy, n = 3) and 5B6 (four copies, n = 2) and their wild type littermates (n = 9). Mice carrying the transgene are significantly smaller in all lines (Statistical significance using Student's t-test P < 0.017 for all lines). All weights were obtained from F1 mice born from a cross between a chimaeric male founder (129/Sv) and a MF1 female. B) Post natal weight data from one to ten weeks of males for the single copy line, 5D3, bred onto the C57/BL6 background for three generation showing persistence of growth retardation after weaning (one copy, Tg n = 9, WT n = 8). C) Weights at 3 weeks of male mice from line 5D3 (one copy, Tg n = 4, WT n = 9) on a 50%:50%; 129/Sv × MF1 background labelled as 5D3/MF1) compared with a 75%:25% background labelled as 5D3/129 (Tg n = 6, WT n = 8). Interaction with a genetic factor within the 129/Sv background results in a more severe growth retardation, increasing from 11.3% to 28.8% (Statistically significant change using Student's t-test. P = 0.014). On a C57BL/6 background, the growth retardation is intermediate at 20.5% (Tg n = 9, WT n = 8). No significant growth retardation is observed in transgenic line 10–15 on a 129/Sv background (Tg n = 8, WT n = 4, P = 0.24). This line carries three copies of the modified BAC where transgenic Cdkn1c is not functional demonstrating that growth retardation is likely due to excess Cdkn1c. C) Comparison of organ weights in wild type and 5D3 transgenic adult males at 8–10 weeks. Growth retardation is not restricted to organs in which there was excess embryonic Cdkn1c WT n = 9 and Tg n = 6). *denotes tissues that were exposed to excess Cdkn1c during embryogenesis.