||Little Mice (GHRHr)
||Longevity data done on C57BL/6J, also commercially available on C57BL/6J.
||GHRHr (growth hormone-releasing hormone receptor)
|Type of change
||Point mutation (Asp60 Gly60)
|Nature of protein
||423-amino acid protein, binds to GHRH and induces growth hormone (GH) secretion.
||Small body size, stunted growth, obesity in late life. Contrary to Ames and Snell dwarf mice, Little mice have normal fertility.
|Corresponding human phenotype
||Isolated growth hormone deficiency.
Online Mendelian Inheritance in Man (OMIM) number for human GHRHr is 139191.
||S. C. Lin et al., Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364, 208-213 (1993).
||Little mice (stock number 000533) are commercially available through the Jackson Laboratory (http://jaxmice.jax.org).
||For more information on Little mice, see below.
||Related transgenic/knockout mice:
Ames Dwarf Mice: http://sageke.sciencemag.org/cgi/content/full/sageke;2001/1/tg11
Snell Dwarf Mice: http://sageke.sciencemag.org/cgi/content/full/sageke;2001/3/tg13
SAGE KE's Genes/Interventions database:
OMIM entry for human GHRHr gene:
||Growth hormone, aging/ageing, life-span, Snell dwarf, Ames dwarf, Little dwarf, GHRHr, GH, insulin-like growth factor 1 (IGF-1).
Little Dwarf Mice
Contrary to Snell and Ames dwarf mice, Little mice are deficient only in growth hormone (GH) and are sufficient in thyroid-stimulating hormone and prolactin. As a result, these mice are fertile, yet are only two-thirds the weight of wild-type littermates when they reach adulthood. Average life-span is extended by 25%, and maximum life-span is extended 15% as compared with wild-type and heterozygous littermates. This extension in life-span seems to be dependent on a low-fat diet. At first glance, the increase in life-span seems smaller than in Ames and Snell mice; however, the sample size used for the determination of longevity in the Little mice was relatively small, so it is possible that life-span extension might be similar to that seen in Ames and Snell mice. If the increase in life-span in Little mice is as great as or close to that in the Ames and Snell mice, one could conclude that the longevity-extending effect in all three different mouse strains is due solely to the GH/insulin-line growth factor 1 (IGF-1) hormonal axis. Further evidence to support this conjecture comes from a preliminary study of the longevity of growth hormone receptor (GHr) knockout mice: Even though the sample size was extremely small, it appears that GHr knockout mice also have an increased life-span.
October 24, 2001
K. T. Coschigano et al., Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141, 2608-2613 (2000).[CrossRef][Medline]
K. Flurkey et al., Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. U.S.A. 98, 6736-6741 (2001).[Abstract/Free Full Text]
S. C. Lin et al., Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364, 208-213 (1993).[CrossRef][Medline]