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A novel ENU-induced mutation, peewee, causes dwarfism in the mouse

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An Erratum to this article was published on 30 July 2009

An Erratum to this article was published on 30 July 2009

Abstract

We identified a novel fertile autosomal recessive mutation called peewee that results in dwarfing, in a region-specific ENU-induced mutagenesis. These mice at litter size were smaller those of other strains. Histological analysis revealed that the major organs appear normal, but abnormalities in cellular proliferation were observed in bone, liver, and testis. Haplotype analysis localized the peewee gene to a 3.3-Mb region between D5Mit83 and D5Mit356.3. There are 18 genes in this linkage area. We also performed in silico mapping using the PosMedSM program, which searches for connections among keywords and genes in an interval, but no similar phenotype descriptions were found for these genes. In the peewee mutant compared to the normal C57BL/6 J mouse, only Slc10a4 expression was lower. Our preliminary mutation analysis examining the nucleotide sequence of three exons, two introns, and an untranslated region of Slc10a4 did not find any sequence difference between the peewee mouse and the C57BL/6 J mouse. Detailed analysis of peewee mice might provide novel molecular insights into the complex mechanisms regulating body growth.

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References

  • Bartke A (1964) Histology of the anterior hypophysis, thyroid and gonads of two types of dwarf mice. Anat Rec 149:225–235

    Article  PubMed  CAS  Google Scholar 

  • Bartke A (1965) Influence of luteotrophin on fertility of dwarf mice. J Reprod Fertil 10:93–103

    Article  PubMed  CAS  Google Scholar 

  • Bartke A (2000) Delayed aging in Ames dwarf mice. Relationships to endocrine function and body size. In: Hekimi S (ed) The molecular genetics of aging. Springer, Berlin

    Google Scholar 

  • Bartke A, Brown-Borg H (2004) Life extension in the dwarf mouse. Curr Top Dev Biol 63:189–225

    Article  PubMed  CAS  Google Scholar 

  • Bartke A, Lloyd CW (1970) Influence of prolactin and pituitary isografts on spermatogenesis in dwarf mice and hypophysectomized rats. J Endocrinol 46:321–329

    Article  PubMed  CAS  Google Scholar 

  • Bartke A, Brown-Borg HM, Bode AM, Carlson J, Hunter WS et al (1998) Does growth hormone prevent or accelerate aging? Exp Gerontol 33:675–687

    Article  PubMed  CAS  Google Scholar 

  • Beamer WJ, Eicher EM, Maltais LJ, Southard JL (1981) Inherited primary hypothyroidism in mice. Science 212:61–63

    Article  PubMed  CAS  Google Scholar 

  • Beamer WG, Maltais LJ, De Baets MH, Eicher EM (1987) Inherited congenital goiter in mice. Endocrinology 120:838–840

    Article  PubMed  CAS  Google Scholar 

  • Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384:33

    Article  PubMed  CAS  Google Scholar 

  • Chandra D, Jia F, Liang J, Peng Z, Suryanarayanan A et al (2006) GABA-A receptor alpha-4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol. Proc Natl Acad Sci USA 103:15230–15235

    Article  PubMed  CAS  Google Scholar 

  • Cheng TC, Beamer WG, Phillips JA III, Bartke A, Mallonee RL et al (1983) Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice. Endocrinology 113:1669–1678

    Article  PubMed  CAS  Google Scholar 

  • Eicher EM, Beamer WG (1976) Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6. J Hered 67:87–91

    PubMed  CAS  Google Scholar 

  • Flamant F, Poguet AL, Plateroti M, Chassande O, Gauthier K et al (2002) Congenital hypothyroid Pax8(−/−) mutant mice can be rescued by inactivating the TRalpha gene. Mol Endocrinol 16:24–32

    Article  PubMed  CAS  Google Scholar 

  • Flurkey K, Papaconstantinou J, Harrison DE (2002) The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mech Ageing Dev 123:121–130

    Article  PubMed  CAS  Google Scholar 

  • 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 USA 98:6736–6741

    Article  PubMed  CAS  Google Scholar 

  • Geyer J, Wilke T, Petzinger E (2006) The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn Schmiedeberg Arch Pharmacol 372:413–431

    Article  CAS  Google Scholar 

  • Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H et al (2004) The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins. Introduction. Pflugers Arch 447:465–468

    Article  PubMed  CAS  Google Scholar 

  • Kano K, Marin de Evsikova C, Young J, Wnek C, Maddatu TP et al (2008) A novel dwarfism with gonadal dysfunction due to loss-of-function allele of the collagen receptor gene, Ddr2, in the mouse. Mol Endocrinol 22:1866–1880

    Article  PubMed  CAS  Google Scholar 

  • Kemp T (1938) Hereditary and endocrine function. Acta Pathol Microbiol Scand 14:290–305

    Google Scholar 

  • Knabl J, Witschi R, Hosl K, Reinold H, Zeilhofer UB et al (2008) Reversal of pathological pain through specific spinal GABA(A) receptor subtypes. Nature 451:330–334

    Article  PubMed  CAS  Google Scholar 

  • Kronenberg HM (2003) Developmental regulation of the growth plate. Nature 423Z:332–336

    Article  CAS  Google Scholar 

  • Li S, Crenshaw EB III, Rawson EJ, Simmons DM, Swanson LW et al (1990) Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347:528–533

    Article  PubMed  CAS  Google Scholar 

  • Sato K, Mano H, Ariyama T, Inazawa J, Yazaki Y et al (1994) Molecular cloning and analysis of the human Tec protein-tyrosine kinase. Leukemia 8:1663–1672

    PubMed  CAS  Google Scholar 

  • Schaiber R, Gowen J (1961) A new dwarf mouse. Genetics 46:896

    Google Scholar 

  • Schimenti J, Bucan M (1998) Functional genomics in the mouse: phenotype-based mutagenesis screens. Genome Res 8:698–710

    PubMed  CAS  Google Scholar 

  • Shinohara M, Koga T, Okamoto K, Sakaguchi S, Arai K et al (2008) Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK and ITAM signals. Cell 132:794–806

    Article  PubMed  CAS  Google Scholar 

  • Sinha YN, Salocks CB, Vanderlaan WP (1975) Pituitary and serum concentrations of prolactin and GH in Snell dwarf mice. Proc Soc Exp Biol Med 150:207–210

    PubMed  CAS  Google Scholar 

  • Smith PE, MacDowell EC (1931) The differential effect of hereditary mouse dwarfism on the anterior pituitary hormones. Anat Rec 50:85–93

    Article  Google Scholar 

  • Snell GD (1929) Dwarf, a new mendelian recessive character of the house mouse. Proc Natl Acad Sci USA 15:733–734

    Article  PubMed  CAS  Google Scholar 

  • Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ et al (1996) Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327–333

    Article  PubMed  CAS  Google Scholar 

  • Sperandeo MP, Annunziata P, Bozzato A, Piccolo P, Maiuri L et al (2007) Slc7a7 disruption causes fetal growth retardation by downregulating Igf1 in the mouse model of lysinuric protein intolerance. Am J Cell Physiol 293:C191–C198

    Article  CAS  Google Scholar 

  • Stephenson DA, Lee KH, Nagle DL, Yen CH, Morrow A et al (1994) Mouse rump-white mutation associated with an inversion of chromosome 5. Mamm Genome 5:342–348

    Article  PubMed  CAS  Google Scholar 

  • Takabayashi S, Umeki K, Yamamoto E, Suzuki T, Okayama A et al (2006) A novel hypothyroid dwarfism due to the missense mutation Arg479Cys of the thyroid peroxidase gene in the mouse. Mol Endocrinol 20:2584–2590

    Article  PubMed  CAS  Google Scholar 

  • van Buul-Offers S (1983) Hormonal and other inherited growth disturbances in mice with special reference to the Snell dwarf mouse. Acta Endocrinol 103:1–47

    Google Scholar 

  • Wilson L, Ching YH, Farias M, Hartford SA, Howell G et al (2005) Random mutagenesis of proximal mouse chromosome 5 uncovers predominantly embryonic lethal mutations. Genome Res 15:1095–1105

    Article  PubMed  CAS  Google Scholar 

  • Yan W, Wu F, Morser J, Wu Q (2000) Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Proc Natl Acad Sci USA 97:8525–8529

    Article  PubMed  CAS  Google Scholar 

  • Yoshida T, Yamanaka K, Atsumi S, Tsumura H, Sasaki R et al (1994) A novel hypothyroid ‘growth-retarded’ mouse derived from Snell’s dwarf mouse. J Endocrinol 142:435–446

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Dr. Neena Haider and Dr. Arne Nystuen for their critiques of the manuscript. This research was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Morinaga Foundation, the Foundation for Growth Science, and the U.S. National Institutes of Health (grants DK46977 and DK73267).

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Authors and Affiliations

  1. Laboratory of Applied Genetics, Graduate School of Agricultural and Life Science, University of Tokyo, Tokyo, 113-8657, Japan

    Lee Bokryeon, Kiyoshi Kano & Kunihiko Naito

  2. The Jackson Laboratory, Bar Harbor, ME, 04609, USA

    Jay Young, Simon W. M. John, Patsy M. Nishina & Jurgen K. Naggert

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  1. Lee Bokryeon
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  2. Kiyoshi Kano
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  3. Jay Young
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  4. Simon W. M. John
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  6. Jurgen K. Naggert
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  7. Kunihiko Naito
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Correspondence to Kiyoshi Kano.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00335-009-9202-9

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Supplementary material 1 (DOCX 17 kb)

Supplementary Fig. 1

The litter sizes of peewee mice and inbred line (EPS 759 kb)

Supplementary Fig. 2

Cross sections of various tissues from peewee mutant, stained with hematoxylin and eosin, at 10 weeks of age. Brain (A), pituitary gland (B), eye (C), heart (D), lung (E), spleen (F), skin (G), skeletal muscle (H), pancreas (I), liver (J), stomach (K), intestine (L), kidney (M), uterus (N), ovary (O), and testis (P). Scale bar = 25 μm (C, D, E), 100 μm (F, G, H, J, K, L), 200 μm (A, B, C, M, N, O, P, Q) (EPS 7217 kb)

Supplementary material 4 (EPS 810 kb)

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Bokryeon, L., Kano, K., Young, J. et al. A novel ENU-induced mutation, peewee, causes dwarfism in the mouse. Mamm Genome 20, 404–413 (2009). https://doi.org/10.1007/s00335-009-9197-2

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  • DOI: https://doi.org/10.1007/s00335-009-9197-2

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