Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C

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Abstract
GROWTH is one of the fundamental aspects in the development of an organism. Classical genetic studies have isolated four viable, spontaneous mouse mutants1 disrupted in growth, leading to dwarfism. Pygmy is unique among these mutants because its phenotype cannot be explained by aberrations in the growth hormone–insulin-like growth factor endocrine pathway2–5. Here we show that the pygmy phenotype arises from the inactivation of Hmgi-c (ref. 6), a member of the Hmgi family7 which function as architectural factors in the nuclear scaffold8 and are critical in the assembly of stereospecific transcriptional complexes9. Hmgi-c and another Hmgi family member, Hmgi(y) (ref. 10), were found to be expressed predominantly during embryogenesis. The HMGI proteins are known to be regulated by cell cycle-dependent phos-phorylation which alters their DNA binding affinity11. These results demonstrate the important role of HMGI proteins in mammalian growth and development.