Figure 2.

Targeted disruption of the Socs7 gene by homologous recombination. (A) Schematic representation of mouse Socs7 gene (top), targeting construct (middle), and targeted allele (bottom). Relevant restriction sites are indicated: Bg, BglII; H, HindIII; N, NotI; S, SalI; X, XbaI. The black boxes indicate exons. Neo^R refers to the positive selection marker. The genomic fragment used as a probe for Southern blot analysis and the expected fragments after BglII digestion are indicated. (B) Southern blot analysis of BglII-digested genomic DNA from ES cell clones. The blot was hybridized with the indicated 3′ external probe. Lanes 1 and 2 show the wild-type allele from MEF and ES cells. Lanes 3–8 are from ES cells with correctly targeted alleles. (C) PCR analysis of genomic DNA from the tails of wild-type, heterozygous (Het), and knockout littermates. (D) Northern blot analysis of liver, skeletal muscle, and testis from wild-type, heterozygous, and knockout mice, showing the absence of Socs7 full-length transcript expression. (E) Growth retardation and hydrocephalus in Socs7 –/ – C57BL/6 mice. At 20 days of age, affected knockout mice exhibited a 40% decrease in weight when compared with heterozygote littermates on the C57BL/6 background (upper panel). Severe hydrocephalus is also present in a 4-week-old Socs7 –/ – mouse (lower panels). Hydrocephalus was not apparent in the mixed-background mice used in this study (image not shown).