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Type Coisogenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Heterozygote (Female x Male) Species laboratory mouse Generation N5F72 (24-DEC-08) Appearance
black, small body size
Related Genotype: a/a Ghrhrlit/Ghrhrlit
black, unaffected
Related Genotype: a/a Ghrhrlit/+Description
Mice homozygous for the little spontaneous mutation (Ghrhrlit) are characterized by a deficiency in pituitary growth hormone and prolactin and growth retardation. Male mice have reduced fertility and female mice show a delay in lactation.Development
The little (Ghrhrlit) mutation arose spontaneously in C57BL/6J at The Jackson Laboratory in 1970. It has been maintained on this background through sibling matings with occasional backcrosses to C57BL/6J. In 1983 C57BL/6J females were bred to heterozygous males to generate embryos for cryopreservation.
| Control | ||
|---|---|---|
| Heterozygote from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying Ghrhrlit allele
002577 B6;CB17-Ghrhrlit Prkdcscid/Bm View Strains carrying Ghrhrlit (1 strain)
Genetic Quality Control Annual Report
JAX® NOTES, Fall 2001; 483. Extended Life Span in Mice with Dwarfing Mutations.
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Ghrhrlit/Ghrhrlit
C57BL/6J-Ghrhrlit
- adipose tissue phenotype
- increased adipose tissue amount (MGI Ref ID J:3735)
- greater amounts than wild-type controls
- endocrine/exocrine gland phenotype
- abnormal lactation (MGI Ref ID J:5647)
- failed milk production with first, but not subsequent, litters
- abnormal somatotroph morphology (MGI Ref ID J:7211)
- decreased somatotroph cell number (MGI Ref ID J:7211)
- decreased somatotroph cell size (MGI Ref ID J:7211)
- decreased somatotroph secretory granule number (MGI Ref ID J:7211)
- some cells are devoid of secretory granules
- absent somatotroph secretory granules (MGI Ref ID J:7211)
- some cells have reduced numbers of secretory granules
- small pituitary gland (MGI Ref ID J:5647)
- growth/size phenotype
- increased susceptibility to age related obesity (MGI Ref ID J:5647)
- postnatal growth retardation (MGI Ref ID J:5647)
- reduced weight, beginning at 2 weeks of age
- homeostasis/metabolism phenotype
- decreased growth hormone level (MGI Ref ID J:5647)
- in the pituitary
- decreased circulating growth hormone level (MGI Ref ID J:3735)
- decreased prolactin level (MGI Ref ID J:5647)
- in the pituitary
- reproductive system phenotype
- abnormal lactation (MGI Ref ID J:5647)
- failed milk production with first, but not subsequent, litters
- reduced male fertility (MGI Ref ID J:5647)
- only 50% sired first litters, only 50% of these sired second litters, third litters rare
- nervous system phenotype
- abnormal somatotroph morphology (MGI Ref ID J:7211)
- decreased somatotroph cell number (MGI Ref ID J:7211)
- decreased somatotroph cell size (MGI Ref ID J:7211)
- decreased somatotroph secretory granule number (MGI Ref ID J:7211)
- some cells are devoid of secretory granules
- absent somatotroph secretory granules (MGI Ref ID J:7211)
- some cells have reduced numbers of secretory granules
- small pituitary gland (MGI Ref ID J:5647)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Ghrhrlit related
Developmental Biology Research
Growth Defects
Endocrine Deficiency Research
Hypothalamus/Pituitary Defects
Mouse/Human Gene Homologs
growth hormone deficiency
| Allele Symbol | Ghrhrlit | ||
|---|---|---|---|
| Allele Name | little | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | lit; litm; | ||
| Strain of Origin | C57BL/6J | ||
| Gene Symbol and Name | Ghrhr, growth hormone releasing hormone receptor | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | GHRFR; GHRHREC; GHRHRpsv; GRFR; Ghrfr; growth hormone releasing factor receptor; lit; little; | ||
| Molecular Note | The mutation in little mice is a A-to-G transition in codon 60 that is predicted to alter this residue from a aspartate to a glycine in the encoded protein. Reduced levels of mRNA were noted in total RNA derived from pituitary of homozygous mice, and invitro assays demonstrated that no functional protein is made from this allele. [MGI Ref ID J:12846] [MGI Ref ID J:13404] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
Bugni JM; Poole TM; Drinkwater NR. 2001. The little mutation suppresses DEN-induced hepatocarcinogenesis in mice and abrogates genetic and hormonal modulation of susceptibility. Carcinogenesis 22(11):1853-62. [PubMed: 11698349] [MGI Ref ID J:72758]
Godfrey P; Rahal JO; Beamer WG; Copeland NG; Jenkins NA; Mayo KE. 1993. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4(3):227-32. [PubMed: 8395283] [MGI Ref ID J:12846]
Lin SC; Lin CR; Gukovsky I; Lusis AJ; Sawchenko PE; Rosenfeld MG. 1993. Molecular basis of the little mouse phenotype and implications for cell type-specific growth [see comments] Nature 364(6434):208-13. [PubMed: 8391647] [MGI Ref ID J:13404]
Obal F Jr; Alt J; Taishi P; Gardi J; Krueger JM. 2003. Sleep in mice with nonfunctional growth hormone-releasing hormone receptors. Am J Physiol Regul Integr Comp Physiol 284(1):R131-9. [PubMed: 12388430] [MGI Ref ID J:82887]
Ghrhrlit relatedBarger JL; Walford RL; Weindruch R. 2003. The retardation of aging by caloric restriction: its significance in the transgenic era. Exp Gerontol 38(11-12):1343-51. [PubMed: 14698815] [MGI Ref ID J:87701]
Beamer WG; Shultz KL; Tennent BJ; Shultz LD. 1993. Granulosa cell tumorigenesis in genetically hypogonadal-immunodeficient mice grafted with ovaries from tumor-susceptible donors. Cancer Res 53(16):3741-6. [PubMed: 8339285] [MGI Ref ID J:14443]
Beamer WH; Eicher EM. 1976. Stimulation of growth in the little mouse. J Endocrinol 71(1):37-45. [PubMed: 978118] [MGI Ref ID J:5710]
Bugni JM; Poole TM; Drinkwater NR. 2001. The little mutation suppresses DEN-induced hepatocarcinogenesis in mice and abrogates genetic and hormonal modulation of susceptibility. Carcinogenesis 22(11):1853-62. [PubMed: 11698349] [MGI Ref ID J:72758]
Bunger L; Hill WG. 1999. Role of growth hormone in the genetic change of mice divergently selected for body weight and fatness. Genet Res 74(3):351-60. [PubMed: 10689811] [MGI Ref ID J:60661]
Cheng TC; Beamer WG; Phillips JA 3d; Bartke A; Mallonee RL; Dowling C. 1983. Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice. Endocrinology 113(5):1669-78. [PubMed: 6194978] [MGI Ref ID J:7211]
Christensen E; Wilson DB. 1981. Fine structure of somatotrophs and mammotrophs in the pituitary pars distalis of the little (lit) mutant mouse. Virchows Arch B Cell Pathol Incl Mol Pathol 37(1):89-96. [PubMed: 6116352] [MGI Ref ID J:15348]
Dickson SL; Doutrelant-Viltart O; Leng G. 1995. GH-deficient dw/dw rats and lit/lit mice show increased Fos expression in the hypothalamic arcuate nucleus following systemic injection of GH-releasing peptide-6. J Endocrinol 146(3):519-26. [PubMed: 7595148] [MGI Ref ID J:29289]
Donahue LR; Beamer WG. 1993. Growth hormone deficiency in 'little' mice results in aberrant body composition, reduced insulin-like growth factor-I and insulin-like growth factor-binding protein-3 (IGFBP-3), but does not affect IGFBP-2, -1 or -4. J Endocrinol 136(1):91-104. [PubMed: 7679139] [MGI Ref ID J:3735]
Donahue LR; Watson G; Beamer WG. 1993. Regulation of metabolic water and protein compartments by insulin-like growth factor-I and testosterone in growth hormone-deficient lit/lit mice. J Endocrinol 139(3):431-9. [PubMed: 7510770] [MGI Ref ID J:16863]
Eicher EM. 1972. lit - little Mouse News Lett 47:36. [MGI Ref ID J:64445]
Eicher EM; Beamer WG. 1976. Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6. J Hered 67(2):87-91. [PubMed: 1270792] [MGI Ref ID J:5647]
Eleswarapu S; Gu Z; Jiang H. 2008. Growth hormone regulation of insulin-like growth factor-I gene expression may be mediated by multiple distal signal transducer and activator of transcription 5 binding sites. Endocrinology 149(5):2230-40. [PubMed: 18276757] [MGI Ref ID J:136020]
Fleenor D; Oden J; Kelly PA; Mohan S; Alliouachene S; Pende M; Wentz S; Kerr J; Freemark M. 2005. Roles of the lactogens and somatogens in perinatal and postnatal metabolism and growth: studies of a novel mouse model combining lactogen resistance and growth hormone deficiency. Endocrinology 146(1):103-12. [PubMed: 15388648] [MGI Ref ID J:95779]
Flurkey K; Papaconstantinou J; Miller RA; Harrison DE. 2001. 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(12):6736-41. [PubMed: 11371619] [MGI Ref ID J:69878]
Foster MP; Jensen ER; Montecino-Rodriguez E; Leathers H; Horseman N; Dorshkind K. 2000. Humoral and cell-mediated immunity in mice with genetic deficiencies of prolactin, growth hormone, insulin-like growth factor-I, and thyroid hormone. Clin Immunol 96(2):140-9. [PubMed: 10900161] [MGI Ref ID J:63735]
Gaylinn BD; Dealmeida VI; Lyons CE Jr; Wu KC; Mayo KE; Thorner MO. 1999. The mutant growth hormone-releasing hormone (GHRH) receptor of the little mouse does not bind GHRH. Endocrinology 140(11):5066-74. [PubMed: 10537133] [MGI Ref ID J:58346]
Godfrey P; Rahal JO; Beamer WG; Copeland NG; Jenkins NA; Mayo KE. 1993. GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4(3):227-32. [PubMed: 8395283] [MGI Ref ID J:12846]
Greenhalgh CJ; Rico-Bautista E; Lorentzon M; Thaus AL; Morgan PO; Willson TA; Zervoudakis P; Metcalf D; Street I; Nicola NA; Nash AD; Fabri LJ; Norstedt G; Ohlsson C; Flores-Morales A; Alexander WS; Hilton DJ. 2005. SOCS2 negatively regulates growth hormone action in vitro and in vivo. J Clin Invest 115(2):397-406. [PubMed: 15690087] [MGI Ref ID J:95918]
Herington AC; Harrison D; Graystone J. 1983. Hepatic binding of human and bovine growth hormones and ovine prolactin in the dwarf little mouse. Endocrinology 112(6):2032-8. [PubMed: 6303755] [MGI Ref ID J:7060]
Iida K; Del Rincon JP; Kim DS; Itoh E; Nass R; Coschigano KT; Kopchick JJ; Thorner MO. 2004. Tissue-specific regulation of growth hormone (GH) receptor and insulin-like growth factor-I gene expression in the pituitary and liver of GH-deficient (lit/lit) mice and transgenic mice that overexpress bovine GH (bGH) or a bGH antagonist. Endocrinology 145(4):1564-70. [PubMed: 14726438] [MGI Ref ID J:105653]
Iida K; Itoh E; Kim DS; del Rincon JP; Coschigano KT; Kopchick JJ; Thorner MO. 2004. Muscle mechano growth factor is preferentially induced by growth hormone in growth hormone-deficient lit/lit mice. J Physiol 560(Pt 2):341-9. [PubMed: 15308683] [MGI Ref ID J:133848]
Iida K; del Rincon JP; Kim DS; Itoh E; Coschigano KT; Kopchick JJ; Thorner MO. 2004. Regulation of full-length and truncated growth hormone (GH) receptor by GH in tissues of lit/lit or bovine GH transgenic mice. Am J Physiol Endocrinol Metab 287(3):E566-73. [PubMed: 15165994] [MGI Ref ID J:133236]
Ikushima H; Kanaoka M; Kojima S. 2003. Cutting edge: Requirement for growth hormone-releasing hormone in the development of experimental autoimmune encephalomyelitis. J Immunol 171(6):2769-72. [PubMed: 12960295] [MGI Ref ID J:85381]
Itoh E; Iida K; del Rincon JP; Kim DS; Thorner MO. 2004. Diurnal variation in growth hormone receptor messenger ribonucleic acid in liver and skeletal muscle of lit/+ and lit/lit mice. Endocr J 51(6):529-35. [PubMed: 15644570] [MGI Ref ID J:103494]
Jansson JO; Downs TR; Beamer WG; Frohman LA. 1986. Receptor-associated resistance to growth hormone-releasing factor in dwarf little mice. Science 232(4749):511-2. [PubMed: 3008329] [MGI Ref ID J:8252]
Johnson D; al-Shawi R; Bishop JO. 1995. Sexual dimorphism and growth hormone induction of murine pheromone-binding proteins. J Mol Endocrinol 14(1):21-34. [PubMed: 7772239] [MGI Ref ID J:24099]
Kasukawa Y; Baylink DJ; Guo R; Mohan S. 2003. Evidence that sensitivity to growth hormone (GH) is growth period and tissue type dependent: studies in GH-deficient lit/lit mice. Endocrinology 144(9):3950-7. [PubMed: 12933669] [MGI Ref ID J:85595]
Lehman DM; Hale DE; Cody JT; Harrison JM; Leach RJ. 1999. Molecular, morphometric and functional analyses demonstrate that the growth hormone deficient little mouse is not hypomyelinated. Brain Res Dev Brain Res 116(2):191-9. [PubMed: 10521563] [MGI Ref ID J:57626]
Liang H; Masoro EJ; Nelson JF; Strong R; McMahan CA; Richardson A. 2003. Genetic mouse models of extended lifespan. Exp Gerontol 38(11-12):1353-64. [PubMed: 14698816] [MGI Ref ID J:87700]
Lin SC; Lin CR; Gukovsky I; Lusis AJ; Sawchenko PE; Rosenfeld MG. 1993. Molecular basis of the little mouse phenotype and implications for cell type-specific growth [see comments] Nature 364(6434):208-13. [PubMed: 8391647] [MGI Ref ID J:13404]
Majeed N; Blouin MJ; Kaplan-Lefko PJ; Barry-Shaw J; Greenberg NM; Gaudreau P; Bismar TA; Pollak M. 2005. A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model. Oncogene 24(29):4736-40. [PubMed: 15870705] [MGI Ref ID J:99544]
Mohan S; Baylink DJ; Srivastava AK. 2008. A chemical mutagenesis screen to identify modifier genes that interact with growth hormone and TGF-beta signaling pathways. Bone 42(2):388-95. [PubMed: 18063435] [MGI Ref ID J:141536]
Montecino-Rodriguez E; Clark RG; Powell-Braxton L; Dorshkind K. 1997. Primary B cell development is impaired in mice with defects of the pituitary/thyroid axis. J Immunol 159(6):2712-9. [PubMed: 9300691] [MGI Ref ID J:110683]
Niermann GL; Watson GL. 1999. Growth hormone and insulin-like growth factor-I enhance beta-glucuronidase gene activation by androgen in mouse kidney. Mol Cell Endocrinol 153(1-2):47-55. [PubMed: 10459853] [MGI Ref ID J:56310]
Nissley SP; Knazek RA; Wolff GL. 1980. Somatomedin activity in sera of genetically small mice. Horm Metab Res 12(4):158-64. [PubMed: 7390396] [MGI Ref ID J:6340]
Obal F Jr; Alt J; Taishi P; Gardi J; Krueger JM. 2003. Sleep in mice with nonfunctional growth hormone-releasing hormone receptors. Am J Physiol Regul Integr Comp Physiol 284(1):R131-9. [PubMed: 12388430] [MGI Ref ID J:82887]
Pati D; Zhang N; Plon SE. 2002. Linking sister chromatid cohesion and apoptosis: role of rad21. Mol Cell Biol 22(23):8267-77. [PubMed: 12417729] [MGI Ref ID J:80123]
Phelps CJ. 1994. Pituitary hormones as neurotrophic signals: anomalous hypophysiotrophic neuron differentiation in hypopituitary dwarf mice. Proc Soc Exp Biol Med 206(1):6-23. [PubMed: 7910409] [MGI Ref ID J:18152]
Phillips JA 3d; Beamer WG; Bartke A. 1982. Analysis of growth hormone genes in mice with genetic defects of growth hormone expression. J Endocrinol 92(3):405-7. [PubMed: 7069343] [MGI Ref ID J:6741]
Puche RC; Alloatti R; Chapo G. 2002. Growth and development of male 'little' mice assessed with Parks' theory of feeding and growth. Growth Dev Aging 66(2):71-8. [PubMed: 12537301] [MGI Ref ID J:81023]
Richards RG; Klotz DM; Walker MP; Diaugustine RP. 2004. Mammary gland branching morphogenesis is diminished in mice with a deficiency of insulin-like growth factor-I (IGF-I), but not in mice with a liver-specific deletion of IGF-I. Endocrinology 145(7):3106-10. [PubMed: 15059953] [MGI Ref ID J:105630]
Schneider P; Stauber M; Voide R; Stampanoni M; Donahue LR; Muller R. 2007. Ultrastructural properties in cortical bone vary greatly in two inbred strains of mice as assessed by synchrotron light based micro- and nano-CT. J Bone Miner Res 22(10):1557-70. [PubMed: 17605631] [MGI Ref ID J:141352]
Sharma MC; Agrawal AK; Sharma MR; Shapiro BH. 1998. Interactions of gender, growth hormone, and phenobarbital induction on murine Cyp2b expression. Biochem Pharmacol 56(9):1251-8. [PubMed: 9802338] [MGI Ref ID J:50483]
Sharma Y; Flurkey K; Astle CM; Harrison DE. 2005. Mice severely deficient in growth hormone have normal hematopoiesis. Exp Hematol 33(7):776-83. [PubMed: 15963853] [MGI Ref ID J:99029]
Wilson DB; Wyatt DP. 1992. Adrenocorticotropic cell distribution in adult and embryonic pituitaries of the little (lit) mutant mouse. Anat Embryol (Berl) 186(4):347-53. [PubMed: 1329576] [MGI Ref ID J:15586]
Wilson DB; Wyatt DP. 1986. Growth hormone and prolactin immunoreactivity in the pituitary gland of postnatal little (lit) mice. Histol Histopathol 1(4):309-13. [PubMed: 2980124] [MGI Ref ID J:802]
Wilson DB; Wyatt DP. 1992. Histopathology of the pituitary gland in neonatal little (lit) mutant mice. Histol Histopathol 7(3):451-5. [PubMed: 1504465] [MGI Ref ID J:3198]
Wong JH; Dukes J; Levy RE; Sos B; Mason SE; Fong TS; Weiss EJ. 2008. Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns. J Clin Invest 118(8):2969-78. [PubMed: 18618017] [MGI Ref ID J:140880]
Woodall SM; Breier BH; O'Sullivan U; Gluckman PD. 1991. The effect of the frequency of subcutaneous insulin-like growth factor-1 administration on weight gain in growth hormone deficient mice. Horm Metab Res 23(12):581-4. [PubMed: 1778592] [MGI Ref ID J:1793]
del Rincon JP; Iida K; Gaylinn BD; McCurdy CE; Leitner JW; Barbour LA; Kopchick JJ; Friedman JE; Draznin B; Thorner MO. 2007. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes 56(6):1638-46. [PubMed: 17363744] [MGI Ref ID J:126470]
Animal Health Reports
Room Number AX11
Colony Maintenance
Mating System Homozygote x Heterozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse Price $128.60 Female or Male Homozygous for Ghrhrlit
Pairs /Price (US dollars $) Pair Genotype $252.70 Homozygous for Ghrhrlit x Heterozygous for Ghrhrlit
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse Price $167.20 Female or Male Homozygous for Ghrhrlit
Pairs /Price (US dollars $) Pair Genotype $328.60 Homozygous for Ghrhrlit x Heterozygous for Ghrhrlit
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Heterozygote from the colony | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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