Simon Horvat, and Juan F. Medrano

Genomics 72, 209–212 (2001)

Cover photo:  Two 11 week old male mice. The larger mouse (44.2 g) to the left is a high-growth, C57BL/6J-hghg, homozygous for a deletion in mouse chromosome 10 that includes the hg gene. The smaller mouse (24.9 g) to the right is a normal C57BL/6J of the same age.
(Photo by Debbie Aldrige, Mediaworks, Univ. of California, Davis.)

  High Growth Phenotype

The high growth (hg) mutation in mouse causes a major increase in growth (30-50% in homozygotes) that is proportional in all tissues and organs and does not result in obesity. High growth (HG) mice are on average 13% leaner but much higher in weight than controls at the same age. This effect is particularly noticeable when control and HG mice are fed high-energy diets. The mutation alters energy metabolism by increasing efficiency of growth and/or decreasing maintenance energy requirements. The effects of the mutation are detected early in development, manifested by delayed muscular cell fusion and an increase in muscle fiber number. Interestingly, HG mice have lower concentrations of Growth Hormone (GH) but much higher concentrations of Insulin-like Growth Factor I (IGF-I) in their plasma than normal mice. 

 hg was initially localized by interval mapping to the distal half of mouse chromosome 10 and then mapped hg to a 500-kb deletion. We have sequenced this region and identified that the deletion breakpoint of HG mice occurs in intron 2 of the Socs2/Cish2 (suppressor of cytokine signaling 2/cytokine-inducible SH2-containing protein 2).  Socs2 is not expressed in HG mice  and we have identify Socs2 as the causative gene of the HG phenotype (Genomics 72:209-212, 2001).