SP-C targeting construct and Southern blot identification of targeted
ES cells and mice. (A) A restriction map of the SP-C
gene is shown above the targeting vector. Exons are numbered 1–6. The
bottom line diagrams the targeted SP-C gene. Precise homologous
recombination between lines 1 and 2 results in exon 2 interrupted by
the neomycin resistance (pGKneo) gene and loss of the nonhomologous
herpes simplex virus thymidine kinase (HSV-TK) gene (bottom line).
(B) Southern blot analysis of Bsu36I
genomic DNA from ES cells. Bsu36I-digested DNA was
probed with a 5′ Sph-Pst fragment adjacent to the targeting DNA, which
detects 3.7-kb upstream and 5.5-kb downstream endogenous
bands (+/+, lane 1). DNA from a targeted ES cell colony (+/−)
shows the 5.5-kb allele and the targeted allele that are increased by
the size of the inserted pGKneo cassette to 7.2 kb. (C)
Southern blot analysis of genomic DNA from SP-C gene-targeted mice. The
5′ probe was used for blots of BglII-digested DNA. A
single, 5.7-kb BglII band is detected in wild-type mice
by the 5′ probe. Two bands are detected in mice heterozygous for the
targeted site (+/−). Homozygous SP-C (−/−) mice produce only the
7.4-kb, larger upper band, indicating that both SP-C alleles are
interrupted.