Figure 1

Inactivation of the γ ₁ subunit by gene targeting. A) i. The normal γ₁ gene, which contains 4 exons (represented by black boxes). ii. The targeting vector contains a fragment with 4.4 kb of homology to a region 5' of exon 1 and a 2.6 kb fragment with homology to a region 3' of exon 4 (thick horizontal lines). These fragments are separated by the neo gene, which is used to select the ES cells in culture. iii. The modified γ₁ locus. When recombination occurs in the regions indicated by the X's, all 4 exons of the γ₁ gene are replaced by the neo cassette. B, C) Southern blots of DNA, either digested with Eco RI and hybridized to probe 1 (B), or DNA digested with Hind III and hybridized to probe 2 (C), from control (+/+), γ₁ het (+/-) and γ₁ null (-/-) mice. These data show the predicted size bands for the wild type and targeted alleles. D) Western blots for each of the four skeletal DHPR subunits from control (+/+), γ₁ het (+/-) and γ₁ null (-/-) mice. The γ₁ subunit is absent from the γ₁ null mice and at approximately half the normal level in the γ₁ het mice.