Sci. Aging Knowl. Environ., 24 October 2001
Vol. 2001, Issue 4, p. tg14

GENETICALLY ALTERED MICE

Little Mice

http://sageke.sciencemag.org/cgi/content/full/sageke;2001/4/tg14


Mouse Little Mice (GHRHr)
Genetic background Longevity data done on C57BL/6J, also commercially available on C57BL/6J.
Gene changed 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.
Phenotype 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.
Primary reference S. C. Lin et al., Molecular basis of the little mouse phenotype and implications for cell type-specific growth. Nature 364, 208-213 (1993).
Additional references See below.
Source Little mice (stock number 000533) are commercially available through the Jackson Laboratory (http://jaxmice.jax.org).
Other comments For more information on Little mice, see below.
Other links 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:
http://sageke.sciencemag.org/cgi/genedata/sagekeGdbGene;61
OMIM entry for human GHRHr gene:
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=139191
Keywords Growth hormone, aging/ageing, life-span, Snell dwarf, Ames dwarf, Little dwarf, GHRHr, GH, insulin-like growth factor 1 (IGF-1).
Prepared by Florian Muller

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.

Florian Muller

October 24, 2001

  1. 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]
  2. 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]
  3. 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]








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