Table 2.
Genetic interaction between Grhl3 and Vangl2Lp alleles results in severe SB
| Spinal Phenotype % (n) | ||||
|---|---|---|---|---|
| Genotype | No. embryos | Straight tail | TFDs | SB & TFDs |
|
||||
| Vangl2+/+;Grhl3ct/+ | 4 | 100 (4) | 0 (0) | 0 (0) |
| Vangl2+/+;Grhl3ct/+;TgGrhl3/0 | 11 | 55 (6) | 45 (5) | 0 (0) |
| Vangl2Lp/+;Grhl3ct/+ | 12 | 8 (1) | 92 (11) | 0 (0) |
| Vangl2Lp/+;Grhl3ct/+ TgGrhl3 | 13 | 0 (0) | 23 (3) | 77 (10)* |
| ||||
| Vangl2+/+;Grhl3ct/+ | 14 | 86 (12) | 14 (2) | 0 (0) |
| Vangl2+/+;Grhl3ct/ct | 11 | 55 (6) | 45 (5) | 0 (0) |
| Vangl2+/+;Grhl3ct/+;TgGrhl3/0 | 9 | 78 (7) | 22 (2) | 0 (0) |
| Vangl2+/+;Grhl3ct/ct;TgGrhl3/0 | 8 | 88 (7) | 12 (1) | 0 (0) |
| Vangl2Lp/+;Grhl3ct/+ | 6 | 0 (0) | 100 (6) | 0 (0) |
| Vangl2Lp/+;Grhl3ct/ct | 9 | 0 (0) | 22 (2) | 78 (7) |
| Vangl2Lp/+;Grhl3ct/+;TgGrhl3 | 11 | 0 (0) | 82 (9) | 18 (2) |
| Vangl2Lp/+;Grhl3ct/ct;TgGrhl3 | 11 | 0 (0) | 55 (6) | 45 (5) |
(a) Among experimental litters generated by intercross of Grhl3ct/ct;TgGrhl3/0 with Vangl2Lp/+, SB occurred at high frequency in embryos carrying both the Grhl3 transgene and the Vangl2Lp allele, but was not observed among embryos carrying either allele alone (*P < 0.05; Chi square). (b) Embryos that are heterozygous or homozygous for the Grhl3ct allele but are wild type for Vangl2 display partially penetrant TFDs. Doubly heterozygous (Vangl2Lp/+;Grhl3ct/+) embryos display TFDs, correlating with 100% penetrance of this defect among Lp/+ mice. SB occurs with high frequency among Lp/+;Grhl3ct/ct embryos as reported previously (38). Unlike our finding in Grhl3ct/ct (Gustavsson et al., 2007) and Grhl3-/- embryos (Table 1), this defect is not rescued by the Grhl3 transgene supporting the hypothesis that SB in embryos carrying the Vangl2Lp and Grhl3 transgene, results from an additive genetic interaction. Litters analysed at E11.5 (n = 6 and 9 litters in a and b, respectively).