Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+2p (20-FEB-05) Generation Definitions   Donating Investigator Andrew P McMahon,   University of Southern California

Description
Mice that are heterozygous for the targeted allele are viable and fertile. Mice homozygous for this mutation have a lethal phenotype. Half of homozygous null mice have an embryonic lethal phenotype, dying between 10.5 to 12.5 days post coitum. The cause of embryonic death may be due to circulatory abnormalities. Embryonic death also occurred in late gestation, with the remaining homozygous mutants dying at birth, due to respiratory failure. At 12.5 dpc, initial cartilaginous primordia of mutant embryos forelimbs are not abnormal, but by 13.5 dpc, mutant embryos display severe foreshortening of the forelimbs. At birth, the length of long bones of mutant animals are only one third the length of long bones of wildtype animals. Mutants have reduced chondrocyte proliferation, abnormal chondrocyte maturation and absence of mature osteoblasts in endochondral bones. Recent studies have linked mutations of Ihh to brachydactyly type A-1 St-Jacques. This mutant mouse strain represents a model that may be useful in studies of skeletal morphogenesis.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to replace the entire first exon, encoding much of the signaling peptide, and approximately 1kb of flanking sequence. The construct was electroporated into 129 derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 derived blastocysts. The resulting chimeric animals were backcrossed to 129X1 mice.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Pancreas, Annular

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Acrocapitofemoral Dysplasia; ACFD   (IHH) Brachydactyly, Type A1; BDA1   (IHH)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Ihh^tm1Amc/Ihh^tm1Amc

        involves: 129S1/Sv * 129X1/SvJ

• growth/size phenotype
• decreased body height
  • at birth, homozygotes are consistently shorter than wild-type mice   (MGI Ref ID J:57297)
• disproportionate dwarf
  • at birth mutants display severe short-limb dwarfism   (MGI Ref ID J:89228)
• skeleton phenotype
• abnormal bone ossification
  • in homozygotes, appendicular skeletal elements fail to ossify   (MGI Ref ID J:57297)
• • abnormal bone mineralization
    • at 16.5 dpc, mutant humeri show ectopic initial calcification in the center of cartilage only, suggesting that mineralization occurs in cartilage and not in association with a bone collar   (MGI Ref ID J:57297)
    • by 18.5 dpc, ectopic calcification extends closer to the articular surfaces in mutant bones, including the humerus, sternum, vertebrae, and cartilaginous synchondroses of the base of the skull   (MGI Ref ID J:57297)
  • delayed endochondral bone ossification
    • homozygotes exhibit absence of endochondral bone formation prior to birth   (MGI Ref ID J:57297)
    • in homozygous newborns, most endochondral bones are shorter and relatively malformed   (MGI Ref ID J:57297)
• abnormal skeleton morphology
  • in homozygotes, most skeletal elements are present in the right position and in the right number; however, all elements of the axial and appendicular skeletons exhibit dwarfism   (MGI Ref ID J:57297)
• • abnormal axial skeleton morphology   (MGI Ref ID J:57297)
  • • abnormal rib morphology
      • mutant ribs do not display excessive calcification   (MGI Ref ID J:57297)
    • • short ribs
        • homozygotes have significantly shortened ribs   (MGI Ref ID J:57297)
    • domed cranium
      • at birth, homozygotes show a rounded skull   (MGI Ref ID J:57297)
    • short mandible
      • at birth, homozygotes display a foreshortened mandible   (MGI Ref ID J:57297)
  • abnormal chondrocyte morphology
    • premature chondrocyte hypertrophy, resulting in depletion of non-mineralized cartilage at articular ends of long bones   (MGI Ref ID J:73071)
    • decrease in chondrocyte proliferation at E14.5   (MGI Ref ID J:73071)
    • homozygotes display ectopic maturation of chondrocytes: chondrocyte differentiation is initially delayed, but when it occurs, hypertrophic cells fail to exhibit a stacked columnar organization and occupy inappropriate positions close to articular surfaces   (MGI Ref ID J:57297)
  • abnormal joint morphology
    • at 18.5 dpc, homozygotes show abnormal joint formation   (MGI Ref ID J:57297)
  • abnormal long bone morphology
    • depletion of non-mineralized cartilage at articular ends of long bones   (MGI Ref ID J:73071)
    • mutant long bones fail to show any signs of calcification at 14.5 dpc, as expected; instead, calcification is first noted at 16.5 dpc in mutant scapula and humerus, and slightly later in radius and ulna   (MGI Ref ID J:57297)
  • • abnormal humerus morphology
      • at 18.5 dpc, the mutant humerus and ulna remain partly fused   (MGI Ref ID J:57297)
      • at 18.5 dpc, mutant humeri display no identifiable cortical bone, even in vascularized areas of the perichondrium   (MGI Ref ID J:57297)
    • • short humerus   (MGI Ref ID J:73071)
    • decreased length of long bones
      • at birth, mutant long bones are one-third the length of wild-type long bones   (MGI Ref ID J:57297)
    • • short fibula   (MGI Ref ID J:73071)
      • short humerus   (MGI Ref ID J:73071)
      • short tibia
        • growth retardation of tibia   (MGI Ref ID J:73071)
      • short ulna   (MGI Ref ID J:73071)
  • abnormal skeleton development
    • skeletal growth retardation   (MGI Ref ID J:73071)
  • • abnormal cartilage development
      • although initial cartilage elements develop normally, 13.5-dpc mutant forelimbs show a slight reduction in each cartilage element relative to wild-type; this size difference is clearly visible at 14.5 dpc   (MGI Ref ID J:57297)
    • • abnormal long bone epiphyseal plate proliferative zone
        • as early as 12.5 dpc, mutant humeri show a ~50% reduction in chondrocyte proliferation; in addition, the length of proliferative zone is severely reduced   (MGI Ref ID J:57297)
      • chondrodystrophy
        • reduced chondrocyte proliferation and severe short-limb dwarfism are seen   (MGI Ref ID J:89228)
      • decreased width of hypertrophic chondrocyte zone
        • at 13.5 dpc, mutant humeri show absence of typical hypertrophic chondrocytes   (MGI Ref ID J:57297)
        • at 14.5 dpc, some hypertrophic cells are found in the center of mutant humeri but are neither as large nor as well-organized as those of wild-type bones   (MGI Ref ID J:57297)
        • such hypertrophic cells are surrounded by less mature chondrocytes and show no signs of vascularization or cortical bone formation   (MGI Ref ID J:57297)
  • abnormal trabecular bone morphology
    • 18.5 dpc, mutant humeri display no identifiable trabecular bone in the primary spongiosa   (MGI Ref ID J:57297)
  • decreased osteoblast cell number
    • at 18.5 dpc, homozygotes show no osteocalcin expression in endochondral bones of the appendicular or axial skeleton, indicating absence of mature osteoblasts in mutant long bones   (MGI Ref ID J:57297)
    • in contrast, mature osteoblasts are present in mutant bones formed by intramembranous ossification (e.g. flat bones of the skull, mandible, and clavicle)   (MGI Ref ID J:57297)
  • fused carpal bones
    • at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused   (MGI Ref ID J:57297)
  • short scapula
    • length of scapula is shorter   (MGI Ref ID J:73071)
• limbs/digits/tail phenotype
• abnormal digit morphology
  • failure of digit segmentation and ossification   (MGI Ref ID J:73071)
  • homozygotes display failure of digit segmentation: at 18.5 dpc, mutant digits remain unsegmented and uncalcified   (MGI Ref ID J:57297)
• abnormal forelimb morphology
  • at 13.5 dpc, homozygotes display visibly shortened forelimbs   (MGI Ref ID J:57297)
• • abnormal humerus morphology
    • at 18.5 dpc, the mutant humerus and ulna remain partly fused   (MGI Ref ID J:57297)
    • at 18.5 dpc, mutant humeri display no identifiable cortical bone, even in vascularized areas of the perichondrium   (MGI Ref ID J:57297)
  • • short humerus   (MGI Ref ID J:73071)
  • short ulna   (MGI Ref ID J:73071)
• fused carpal bones
  • at 18.5 dpc, some of the wrist bones of homozygotes appear partly fused   (MGI Ref ID J:57297)
• short fibula   (MGI Ref ID J:73071)
• short limbs
  • 60-80% reduction in the length of the stylopod and the zeugopod at birth   (MGI Ref ID J:73071)
  • at 13.5 dpc, homozygotes display visibly shortened forelimbs   (MGI Ref ID J:57297)
  • at birth, homozygotes display significant dwarfism of the limbs   (MGI Ref ID J:57297)
• short tail   (MGI Ref ID J:57297)
• short tibia
  • growth retardation of tibia   (MGI Ref ID J:73071)
• vision/eye phenotype
• *normal* vision/eye phenotype
  • no rosettes are observed in the retina   (MGI Ref ID J:78708)
  • astrocyte precursor cells at the optic disc and in the optic nerve develop normally   (MGI Ref ID J:83530)
• mortality/aging
• complete neonatal lethality
  • homozygotes that develop to term die at birth due to respiratory failure   (MGI Ref ID J:57297)
• partial embryonic lethality during organogenesis
  • about 50% of homozygotes die at midgestation between 10.5 and 12.5 dpc, probably as a result of circulatory defects   (MGI Ref ID J:57297)
  • some lethality also occurs at later stages of gestation   (MGI Ref ID J:57297)
• craniofacial phenotype
• domed cranium
  • at birth, homozygotes show a rounded skull   (MGI Ref ID J:57297)
• short mandible
  • at birth, homozygotes display a foreshortened mandible   (MGI Ref ID J:57297)
• short snout
  • at birth, homozygotes show a foreshortened snout   (MGI Ref ID J:57297)
• respiratory system phenotype
• respiratory failure   (MGI Ref ID J:57297)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ihh^tm1Amc/Ihh⁺

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• skeleton phenotype
• decreased long bone epiphyseal plate size
  • modest shortening of the growth plate   (MGI Ref ID J:99641)

Ihh^tm1Amc/Ihh^tm1Amc

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

• digestive/alimentary phenotype
• *normal* digestive/alimentary phenotype
  • at 18.5 dpc, homozygotes exhibit no intestinal transformation of the stomach epithelium   (MGI Ref ID J:62158)
• • abnormal digestive system morphology
    • at 18.5 dpc, homozygotes display a smaller gastrointestinal tract relative to wild-type   (MGI Ref ID J:62158)
  • • abnormal digestive organ placement
      • at 18.5 dpc, all homozygotes display an obvious malrotation of the gut, in the absence of reversions in gut situs   (MGI Ref ID J:62158)
    • abnormal small intestine morphology
      • at 18.5 dpc, homozygotes show a significant dilation of the small intestine   (MGI Ref ID J:62158)
      • at 18.5 dpc, homozygotes show a 34% reduction in thickness of the circular smooth muscle layer along the small intestine   (MGI Ref ID J:62158)
      • at this stage, the size of mutant villi is markedly reduced concomitant with a 54% decrease in epithelial stem cell proliferation between and at the base of villi   (MGI Ref ID J:62158)
    • • abnormal duodenum morphology
        • at 18.5 dpc, homozygotes show a 45% reduction in the number of cholecystokinin-producing cells of the duodenum   (MGI Ref ID J:62158)
        • at 18.5 dpc, no duodenal stenosis is observed   (MGI Ref ID J:62158)
    • megacolon
      • at 18.5 dpc, homozygotes display a significant dilation of parts of the colon as well as a thin wall   (MGI Ref ID J:62158)
    • • aganglionic megacolon
        • at 18.5 dpc, 50% of homozygotes display an aganglionic megacolon   (MGI Ref ID J:62158)
• growth/size phenotype
• decreased fetal size
  • at 18.5 dpc, mutant embryos have an overall reduced size relative to wild-type embryos   (MGI Ref ID J:62158)
• nervous system phenotype
• absent enteric neurons
  • at 18.5 dpc, enteric neurons are completely absent along parts of the small intestine and in dilated portions of the colon   (MGI Ref ID J:62158)
• endocrine/exocrine gland phenotype
• annular pancreas
  • at 18.5 dpc, 43% of homozygotes exhibit an annular pancreas   (MGI Ref ID J:62158)
• muscle phenotype
• abnormal smooth muscle morphology
  • at 18.5 dpc, homozygotes show a 34% reduction in thickness of the circular smooth muscle layer along the small intestine   (MGI Ref ID J:62158)

Ihh^tm1Amc/Ihh^tm1Amc

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• embryogenesis phenotype
• abnormal visceral yolk sac morphology   (MGI Ref ID J:128367)
• abnormal vitelline vasculature morphology
  • yolk sacs have fewer and thinner blood vessels compared to wild-type at E9.5   (MGI Ref ID J:128367)
• cardiovascular system phenotype
• abnormal vitelline vasculature morphology
  • yolk sacs have fewer and thinner blood vessels compared to wild-type at E9.5   (MGI Ref ID J:128367)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Ihh^tm1Amc related

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete
Perinatal Lethality
      Homozygous

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ihhtm1Amc
Allele Name		targeted mutation 1, Andrew P McMahon
Allele Type		Targeted (knock-out)
Common Name(s)		Ihh-; Ihhn;
Mutation Made By		Andrew McMahon,   University of Southern California
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Ihh, Indian hedgehog
Chromosome		1
Gene Common Name(s)		BDA1; HHG2;
General Note		Phenotypic Similarity to Human Syndrome: Hirschsprung disease in homozygous mice (J:62158)
Molecular Note		A neomycin resistance cassette replaced the entire first exon, which encodes much of the signaling peptide, and approximately 1kb of flanking sequence. [MGI Ref ID J:57297]

Genotyping

Genotyping Information

Genotyping Protocols

Ihh^tm1Amc, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

St-Jacques B; Hammerschmidt M; McMahon AP. 1999. Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation [published erratum appears in Genes Dev 1999 Oct 1;13(19):2617] Genes Dev 13(16):2072-86. [PubMed: 10465785]  [MGI Ref ID J:57297]

Additional References

Ihh^tm1Amc related

Astorga J; Carlsson P. 2007. Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4. Development 134(20):3753-61. [PubMed: 17881493]  [MGI Ref ID J:128367]

Bren-Mattison Y; Hausburg M; Olwin BB. 2011. Growth of limb muscle is dependent on skeletal-derived Indian hedgehog. Dev Biol 356(2):486-95. [PubMed: 21683695]  [MGI Ref ID J:175458]

Capurro MI; Li F; Filmus J. 2009. Overgrowth of a mouse model of Simpson-Golabi-Behmel syndrome is partly mediated by Indian hedgehog. EMBO Rep 10(8):901-7. [PubMed: 19590577]  [MGI Ref ID J:157333]

Chen MH; Li YJ; Kawakami T; Xu SM; Chuang PT. 2004. Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev 18(6):641-59. [PubMed: 15075292]  [MGI Ref ID J:89228]

Colnot C; de la Fuente L; Huang S; Hu D; Lu C; St-Jacques B; Helms JA. 2005. Indian hedgehog synchronizes skeletal angiogenesis and perichondrial maturation with cartilage development. Development 132(5):1057-67. [PubMed: 15689378]  [MGI Ref ID J:97179]

Dakubo GD; Mazerolle C; Furimsky M; Yu C; St-Jacques B; McMahon AP; Wallace VA. 2008. Indian hedgehog signaling from endothelial cells is required for sclera and retinal pigment epithelium development in the mouse eye. Dev Biol 320(1):242-55. [PubMed: 18582859]  [MGI Ref ID J:139168]

Dakubo GD; Wang YP; Mazerolle C; Campsall K; McMahon AP; Wallace VA. 2003. Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development. Development 130(13):2967-80. [PubMed: 12756179]  [MGI Ref ID J:83530]

Gao B; Hu J; Stricker S; Cheung M; Ma G; Law KF; Witte F; Briscoe J; Mundlos S; He L; Cheah KS; Chan D. 2009. A mutation in Ihh that causes digit abnormalities alters its signalling capacity and range. Nature 458(7242):1196-200. [PubMed: 19252479]  [MGI Ref ID J:147878]

Hebrok M; Kim SK; St Jacques B; McMahon AP; Melton DA. 2000. Regulation of pancreas development by hedgehog signaling. Development 127(22):4905-13. [PubMed: 11044404]  [MGI Ref ID J:65293]

Hojo H; Ohba S; Yano F; Saito T; Ikeda T; Nakajima K; Komiyama Y; Nakagata N; Suzuki K; Takato T; Kawaguchi H; Chung UI. 2012. Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification. J Biol Chem 287(21):17860-9. [PubMed: 22493482]  [MGI Ref ID J:185618]

Hu H; Hilton MJ; Tu X; Yu K; Ornitz DM; Long F. 2005. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132(1):49-60. [PubMed: 15576404]  [MGI Ref ID J:94274]

Joeng KS; Long F. 2009. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development 136(24):4177-85. [PubMed: 19906844]  [MGI Ref ID J:154905]

Karp SJ; Schipani E; St-Jacques B; Hunzelman J; Kronenberg H; McMahon AP. 2000. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development 127(3):543-8. [PubMed: 10631175]  [MGI Ref ID J:59287]

Kesper DA; Didt-Koziel L; Vortkamp A. 2010. Gli2 activator function in preosteoblasts is sufficient to mediate Ihh-dependent osteoblast differentiation, whereas the repressor function of Gli2 is dispensable for endochondral ossification. Dev Dyn 239(6):1818-26. [PubMed: 20503377]  [MGI Ref ID J:160585]

Kobayashi T; Soegiarto DW; Yang Y; Lanske B; Schipani E; McMahon AP; Kronenberg HM. 2005. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest 115(7):1734-42. [PubMed: 15951842]  [MGI Ref ID J:99641]

Koyama E; Ochiai T; Rountree RB; Kingsley DM; Enomoto-Iwamoto M; Iwamoto M; Pacifici M. 2007. Synovial joint formation during mouse limb skeletogenesis: roles of Indian hedgehog signaling. Ann N Y Acad Sci 1116:100-12. [PubMed: 18083924]  [MGI Ref ID J:133905]

Koziel L; Wuelling M; Schneider S; Vortkamp A. 2005. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development 132(23):5249-60. [PubMed: 16284117]  [MGI Ref ID J:102948]

Lenton K; James AW; Manu A; Brugmann SA; Birker D; Nelson ER; Leucht P; Helms JA; Longaker MT. 2011. Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling. Genesis 49(10):784-96. [PubMed: 21557453]  [MGI Ref ID J:178364]

Levi B; James AW; Nelson ER; Brugmann SA; Sorkin M; Manu A; Longaker MT. 2011. Role of Indian hedgehog signaling in palatal osteogenesis. Plast Reconstr Surg 127(3):1182-90. [PubMed: 21364421]  [MGI Ref ID J:182649]

Li X; Blagden CS; Bildsoe H; Bonnin MA; Duprez D; Hughes SM. 2004. Hedgehog can drive terminal differentiation of amniote slow skeletal muscle. BMC Dev Biol 4:9. [PubMed: 15238161]  [MGI Ref ID J:107621]

Long F; Joeng KS; Xuan S; Efstratiadis A; McMahon AP. 2006. Independent regulation of skeletal growth by Ihh and IGF signaling. Dev Biol 298(1):327-33. [PubMed: 16905129]  [MGI Ref ID J:119575]

Long F; Zhang XM; Karp S; Yang Y; McMahon AP. 2001. Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development 128(24):5099-108. [PubMed: 11748145]  [MGI Ref ID J:73071]

Mao J; Kim BM; Rajurkar M; Shivdasani RA; McMahon AP. 2010. Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 137(10):1721-9. [PubMed: 20430747]  [MGI Ref ID J:160363]

Nelson ER; Levi B; Sorkin M; James AW; Liu KJ; Quarto N; Longaker MT. 2011. Role of GSK-3beta in the osteogenic differentiation of palatal mesenchyme. PLoS One 6(10):e25847. [PubMed: 22022457]  [MGI Ref ID J:179587]

Outram SV; Hager-Theodorides AL; Shah DK; Rowbotham NJ; Drakopoulou E; Ross SE; Lanske B; Dessens JT; Crompton T. 2009. Indian hedgehog (Ihh) both promotes and restricts thymocyte differentiation. Blood 113(10):2217-28. [PubMed: 19109233]  [MGI Ref ID J:145997]

Ramalho-Santos M; Melton DA; McMahon AP. 2000. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127(12):2763-72. [PubMed: 10821773]  [MGI Ref ID J:62158]

Shibukawa Y; Young B; Wu C; Yamada S; Long F; Pacifici M; Koyama E. 2007. Temporomandibular joint formation and condyle growth require Indian hedgehog signaling. Dev Dyn 236(2):426-34. [PubMed: 17191253]  [MGI Ref ID J:117221]

Tu X; Joeng KS; Long F. 2012. Indian hedgehog requires additional effectors besides Runx2 to induce osteoblast differentiation. Dev Biol 362(1):76-82. [PubMed: 22155527]  [MGI Ref ID J:180304]

Wang YP; Dakubo G; Howley P; Campsall KD; Mazarolle CJ; Shiga SA; Lewis PM; McMahon AP; Wallace VA. 2002. Development of normal retinal organization depends on Sonic hedgehog signaling from ganglion cells. Nat Neurosci 5(9):831-2. [PubMed: 12195432]  [MGI Ref ID J:78708]

Witte F; Chan D; Economides AN; Mundlos S; Stricker S. 2010. Receptor tyrosine kinase-like orphan receptor 2 (ROR2) and Indian hedgehog regulate digit outgrowth mediated by the phalanx-forming region. Proc Natl Acad Sci U S A 107(32):14211-6. [PubMed: 20660756]  [MGI Ref ID J:163602]

Young B; Minugh-Purvis N; Shimo T; St-Jacques B; Iwamoto M; Enomoto-Iwamoto M; Koyama E; Pacifici M. 2006. Indian and sonic hedgehogs regulate synchondrosis growth plate and cranial base development and function. Dev Biol 299(1):272-82. [PubMed: 16935278]  [MGI Ref ID J:171806]

Zhang XM; Ramalho-Santos M; McMahon AP. 2001. Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R symmetry by the mouse node. Cell 106(2):781-92. [PubMed: 11517919]  [MGI Ref ID J:175111]

Zhang XQ; Afink GB; Hu XR; Nister M; Forsberg-Nilsson K. 2005. Gli1 is not required for Pdgfralpha expression during mouse embryonic development. Differentiation 73(2-3):109-19. [PubMed: 15811134]  [MGI Ref ID J:97242]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	This strain originated and is maintained on a 129 background. The strain is maintained by heterozygous intercrosses. Homozygous lethal.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.