Description

Strain Information

Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x C57BL/6J (000664)         (Female x Male) Mating System C57BL/6J (000664) x Heterozygote         (Female x Male) Species laboratory mouse Generation N88 (07-DEC-07)

Appearance
black with white spotting
Related Genotype: a/a Pax3^Sp/+

Description
Mice homozygous for the splotch spontaneous mutation (Pax3^Sp) die at E13 due to neural tube defects. Malformations of homozygous mutant embryos include rachischisis in the lumbosacral region and frequently in the region of the hindbrain. Heterozygous splotch mice show white spotting on the belly and occasionally on the back, feet, and tail. Splotch is a point mutation within intron 3 of the paired homeobox 3 (Pax3) gene on mouse Chromosome 1. The mutation interferes with normal splicing of intron 3 and leads to at least 4 aberrantly spliced mRNAs with exon 4 deleted. The Pax3^Sp mutation also impairs homodimerization of the protein, a function associated with the octapeptide-encoding central segment of the gene. There are multiple alleles at this locus including splotch-delayed (Pax3^Sp-d, Stock No. 000565), which is similar to splotch but displays caudal rachischisis only.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Pax3^Sp allele

000311	B6-Pax3Sp.Cg-N/J
002902	STOCK Pax3Sp Mlphln/J

View Strains carrying   Pax3^Sp     (2 strains)

Strains carrying other alleles of Pax3

005549	B6;129-Pax3tm1(cre)Joe/J
000565	C57BL/6J-Pax3Sp-d/J

View Strains carrying other alleles of Pax3     (2 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Pax3^Sp/Pax3⁺

        C57BL-Pax3^Sp

• pigmentation phenotype
• white spotting (MGI Ref ID J:12957)
  • occasional spotting on the back and increased spotting on the tail compared to wild-type mice
  • the feet are usually white
• belly spot (MGI Ref ID J:12957)
• skin/coat/nails phenotype
• white spotting (MGI Ref ID J:12957)
  • occasional spotting on the back and increased spotting on the tail compared to wild-type mice
  • the feet are usually white
• belly spot (MGI Ref ID J:12957)

Pax3^Sp/Pax3⁺

        involves: C3HeB * C57BL * C57BL/6J * SWV

• nervous system phenotype
• spina bifida (MGI Ref ID J:114747)
  • increased incidence of spina bifida induced by in utero exposure to 50 mg/kg trans-retinoic acid compared to treated wild-type littermates

Pax3^Sp/Pax3⁺

        involves: C57BL * C57BL/6J * CBA

• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:2179)
  • auditory function and ear morphology are similar to wild type mice auditory function and ear morphology are similar to wild-type mice

Pax3^Sp/Pax3^Sp

        C57BL-Pax3^Sp

• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:12957)
  • die around E14
• nervous system phenotype
• abnormal brain ventricle morphology (MGI Ref ID J:13016)
  • at E10 or later, the lumen of the brain is highly distorted and partially collapsed or obliterated by the excessive overgrowth of neural tissue
  • the lumen in the region of the myelencephalon and rhombencephalon are most sevely affected
• abnormal dorsal root ganglion morphology (MGI Ref ID J:13016)
  • in the region of the anterior limb buds spinal ganglia are absent or greatly reduced in size, disorganized, and abnormally located on the dorsal part of the neural tube
  • the lumbo-sacral region spinal ganglia are usually absent
• abnormal midbrain development (MGI Ref ID J:13016)
  • the lumen in the mesencephalic region is greatly reduced and obscured by neural tissue
  • at E10 and E11, mesencephalic ventricular cells display increased generation time, increased mitotic index, and prolonged mitosis, S phase, and G1
• abnormal neural tube morphology/development (MGI Ref ID J:13016)
  • overgrowth of neural tissue in the region of the open neural tube is variable and becomes more pronounced with age
  • neural overgrowth occurs laterad from the mid-dorsal line of the neural folds
  • ventricular cells in the upper lumbar neural tube and lower lumbar and sacral neural groove contain many gap junctional vesicles that are rarely seen in wild-type or heterozygous mice
• open neural tube (MGI Ref ID J:13016)
  • at E9.5, neural folds are open in the hindlimb region with aggregation of neural tissue on both sides of the dorsal midline
  • at E10 - E12.5, the extent to which the neural fold are open is highly variable ranging from just a small area in the lumbo-sacral region up to from the lumbo-sacral region to the tip of the tail
  • the extent of the area of open neural tube tends to increase in proportion to growth of the embryo
  • open neural folds generally limited to the hindbrain region are seen in about 56% of mice at E10, these are always associated with overgrowth of neural tissue
  • open neural folds in the hindbrain region
• spina bifida (MGI Ref ID J:12957)
• small telencephalic vesicles (MGI Ref ID J:13016)
  • vesicles appear as a network of small channels
• limbs/digits/tail phenotype
• abnormal tail morphology (MGI Ref ID J:13016)
  • distorted shape correlated to degree of rachischisis and neural overgrowth
  • hematomas are frequently found in regions of tail curvature
• kinked tail (MGI Ref ID J:12957)
• pigmentation phenotype
• absent coat pigmentation (MGI Ref ID J:13016)
  • embryonic tissue explants allowed to develop until hair is formed display well developed hairs that are devoid of pigment
• absent skin pigmentation (MGI Ref ID J:13016)
  • embryonic tissue explants allowed to develop until the time when pigment would normally form are devoid of pigment
• skin/coat/nails phenotype
• absent coat pigmentation (MGI Ref ID J:13016)
  • embryonic tissue explants allowed to develop until hair is formed display well developed hairs that are devoid of pigment
• absent skin pigmentation (MGI Ref ID J:13016)
  • embryonic tissue explants allowed to develop until the time when pigment would normally form are devoid of pigment
• cellular phenotype
• increased mitotic index (MGI Ref ID J:13016)
  • at E10 and 11, mesencephalic ventricular cells have increased mitotic index compared to wild-type

Pax3^Sp/Pax3^Sp

        involves: C57BL

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:11996)
  • mice die earlier compared to homozygotes on a congenic C57BR background
  • die around E13-E14
• muscle phenotype
• abnormal myogenesis (MGI Ref ID J:112275)
  • lack myogenic cells in the forming limb buds and hypoglossal cord at E11.5
  • at E10.5 Pax3 expressing cells are absent from the forelimb and hindlimb buds
  • at E12.5 expression of muscle specific markers myogenin and acetylcholinesterase are absent from the forelimb buds and expression of acetylcholinesterase is also absent from the hindlimb buds
  • limb buds from E11 embryos cultured for 4 days fail to generate any cells expressing early myogenic markers (desmin and sarcomeric myosin)
  • however, cells from somites grafted into chick limbs are able to undergo myogenic differentiation
• abnormal dermomyotome development (MGI Ref ID J:112275)
  • foreshortening of the epaxial domain and complete loss of the hypaxial domain of the dermomyotome at E10.5
  • at E9.25, premature termination of the dermamyotome at the same level as the ventral lip of the axial myotome with absence of any epithelial structure in the ventral portion
• abnormal muscle progenitor cell migration (MGI Ref ID J:32016)
  • DiI injections into the 3 somites immediately adjacent to the forelimb bud between E9.25 and E9.5 reveal impaired cell migration with no cell moving more than 30 - 40 um from the site of injection
• nervous system phenotype
• open neural tube (MGI Ref ID J:114748)
  • 10 of 13 had open neural tube in sacro-caudal and cranial regions while in the other 3 the defect was confined to the sacro-caudal region
• spina bifida (MGI Ref ID J:112275)
• hearing/vestibular/ear phenotype
• abnormal bony labyrinth (MGI Ref ID J:114748)
  • all labyrinth structures are abnormal in mice where the neural tube defect extend into the cranial region; however in mice with only sacro-caudal neural tube defects ear morphology is normal
• abnormal endolymphatic duct morphology (MGI Ref ID J:114748)
  • at E10, the origin of endolymphatic duct is shifted backwards and upwards and the duct is shorter and conical in shape
  • at E11 the duct extends backwards and outwards rather than vertically upwards as in wild-type mice
• short endolymphatic duct (MGI Ref ID J:114748)
  • at E10, the endolymphatic duct is shorter than normal
• abnormal otic vesicle formation (MGI Ref ID J:114748)
  • in mice where the neural tube defect extends to the cranial region
• abnormal saccule morphology (MGI Ref ID J:114748)
  • difficult to distinguish and highly abnormal
• abnormal semicircular canal (MGI Ref ID J:114748)
  • present but abnormally located in terms of their planes, point of origin, and relationship to other structures in the labyrinth
• abnormal utricle morphology (MGI Ref ID J:114748)
  • difficult to distinguish and highly abnormal
• decreased cochlear coiling (MGI Ref ID J:114748)
  • at E12 cochlear coiling is poor

Pax3^Sp/Pax3^Sp

        BR.B-Pax3^Sp

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:11996)
  • mice die later compared to mice on a mixed genetic background that includes C57BL
  • die around E18-E19
• nervous system phenotype
• spina bifida (MGI Ref ID J:11996)
  • spina bifida aperta in the lumbosacral area

Pax3^Sp/Pax3^Sp

        involves: 129S2/SvPas * C57BL * C57BL/6J * FVB

• nervous system phenotype
• abnormal embryonic neuroepithelium morphology (MGI Ref ID J:75569)
  • smany apoptotic neuroepithelial cells seen at the site of the neural tube defect
• open neural tube (MGI Ref ID J:75569)
  • seen in all mice
  • treatment with pifithrin-alpha from E8.5 to E9.5 prevented neural tube defects in 55% of embryos

View Research Applications

Research Applications

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

Pax3^Sp related

Dermatology Research
Color and White Spotting Defects

Developmental Biology Research
Neural Crest Defects
Neural Tube Defects

Mouse/Human Gene Homologs
Waardenburg syndrome, type I

Neurobiology Research
Neural Tube Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pax3Sp
Allele Name		splotch
Allele Type		Spontaneous
Common Name(s)		Sp;
Strain of Origin		C57BL
Gene Symbol and Name		Pax3, paired box gene 3
Chromosome		1
Gene Common Name(s)		CDHS; HUP2; MGC120381; MGC120382; MGC120383; MGC120384; MGC134778; Pax-3; Sp; WS1; splotch;
Molecular Note		An A to T transversion at the invariant 3' AG splice acceptor of intron 3 was identified in this allele. This mutation abrogates the normal splicing of intron 3, resulting in the generation of four aberrantly spliced mRNA transcripts. Two of these Pax-3 transcripts make use of cryptic 3' splice sites within the downstream exon, generating small deletions which disrupt the reading frame of the transcripts. A third aberrant splicing event results in the deletion of exon 4, while a fourth retains intron 3. These aberrantly spliced mRNA transcripts are not expected to result in functional Pax3 proteins. [MGI Ref ID J:3731]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Brown CB; Feiner L; Lu MM; Li J; Ma X; Webber AL; Jia L; Raper JA; Epstein JA. 2001. PlexinA2 and semaphorin signaling during cardiac neural crest development. Development 128(16):3071-80. [PubMed: 11688557]  [MGI Ref ID J:71241]

Chalepakis G; Goulding M; Read A; Strachan T; Gruss P. 1994. Molecular basis of splotch and Waardenburg Pax-3 mutations. Proc Natl Acad Sci U S A 91(9):3685-9. [PubMed: 7909605]  [MGI Ref ID J:18260]

Epstein DJ; Vekemans M; Gros P. 1991. Splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67(4):767-74. [PubMed: 1682057]  [MGI Ref ID J:2944]

Epstein DJ; Vogan KJ; Trasler DG; Gros P. 1993. A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant. Proc Natl Acad Sci U S A 90(2):532-6. [PubMed: 8421686]  [MGI Ref ID J:3731]

Epstein JA; Li J; Lang D; Chen F; Brown CB; Jin F; Lu MM; Thomas M; Liu E; Wessels A; Lo CW. 2000. Migration of cardiac neural crest cells in Splotch embryos. Development 127(9):1869-78. [PubMed: 10751175]  [MGI Ref ID J:61431]

Ernest S; Christensen B; Gilfix BM; Mamer OA; Hosack A; Rodier M; Colmenares C; McGrath J; Bale A; Balling R; Sankoff D; Rosenblatt DS; Nadeau JH. 2002. Genetic and molecular control of folate-homocysteine metabolism in mutant mice. Mamm Genome 13(5):259-67. [PubMed: 12016514]  [MGI Ref ID J:76559]

Goulding M; Sterrer S; Fleming J; Balling R; Nadeau J; Moore KJ; Brown SD; Steel KP; Gruss P. 1993. Analysis of the Pax-3 gene in the mouse mutant splotch. Genomics 17(2):355-63. [PubMed: 8406486]  [MGI Ref ID J:13559]

Helmbacher F; Dessaud E; Arber S; deLapeyriere O; Henderson CE; Klein R; Maina F. 2003. Met signaling is required for recruitment of motor neurons to PEA3-positive motor pools. Neuron 39(5):767-77. [PubMed: 12948444]  [MGI Ref ID J:85300]

Houzelstein D; Cheraud Y; Auda-Boucher G; Fontaine-Perus J; Robert B. 2000. The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites. Development 127(10):2155-64. [PubMed: 10769239]  [MGI Ref ID J:61521]

Mansouri A; Stoykova A; Gruss P. 1994. Pax genes in development. J Cell Sci Suppl 18:35-42. [PubMed: 7883790]  [MGI Ref ID J:24468]

Potterf SB; Mollaaghababa R; Hou L; Southard-Smith EM; Hornyak TJ; Arnheiter H; Pavan WJ. 2001. Analysis of sox10 function in neural crest-derived melanocyte development: sox10-dependent transcriptional control of dopachrome tautomerase. Dev Biol 237(2):245-57. [PubMed: 11543611]  [MGI Ref ID J:71587]

Walther C; Guenet JL; Simon D; Deutsch U; Jostes B; Goulding MD; Plachov D; Balling R; Gruss P. 1991. Pax: a murine multigene family of paired box-containing genes. Genomics 11(2):424-34. [PubMed: 1685142]  [MGI Ref ID J:11577]

Pax3^Sp related

Auerbach R. 1954. Analysis of the developmental effects of a lethal mutation in the house mouse. J Exp Zool 127:305-329.  [MGI Ref ID J:13016]

Bajard L; Relaix F; Lagha M; Rocancourt D; Daubas P; Buckingham ME. 2006. A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb. Genes Dev 20(17):2450-64. [PubMed: 16951257]  [MGI Ref ID J:112275]

Bajolle F; Zaffran S; Kelly RG; Hadchouel J; Bonnet D; Brown NA; Buckingham ME. 2006. Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ Res 98(3):421-8. [PubMed: 16397144]  [MGI Ref ID J:118891]

Bennett GD; An J; Craig JC; Gefrides LA; Calvin JA; Finnell RH. 1998. Neurulation abnormalities secondary to altered gene expression in neural tube defect susceptible splotch embryos Teratology 57(1):17-29. [PubMed: 9516748]  [MGI Ref ID J:46128]

Bober E; Franz T; Arnold HH; Gruss P; Tremblay P. 1994. Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells. Development 120(3):603-12. [PubMed: 8162858]  [MGI Ref ID J:17224]

Borycki AG; Li J; Jin F; Emerson CP; Epstein JA. 1999. Pax3 functions in cell survival and in pax7 regulation. Development 126(8):1665-74. [PubMed: 10079229]  [MGI Ref ID J:55248]

Brown CB; Feiner L; Lu MM; Li J; Ma X; Webber AL; Jia L; Raper JA; Epstein JA. 2001. PlexinA2 and semaphorin signaling during cardiac neural crest development. Development 128(16):3071-80. [PubMed: 11688557]  [MGI Ref ID J:71241]

Chalepakis G; Goulding M; Read A; Strachan T; Gruss P. 1994. Molecular basis of splotch and Waardenburg Pax-3 mutations. Proc Natl Acad Sci U S A 91(9):3685-9. [PubMed: 7909605]  [MGI Ref ID J:18260]

Daston G; Lamar E; Olivier M; Goulding M. 1996. Pax-3 is necessary for migration but not differentiation of limb muscle precursors in the mouse. Development 122(3):1017-27. [PubMed: 8631247]  [MGI Ref ID J:32016]

Davidson CE; Li Q; Churchill GA; Osborne LR; McDermid HE. 2007. Modifier locus for exencephaly in Cecr2 mutant mice is syntenic to the 10q25.3 region associated with neural tube defects in humans. Physiol Genomics 31(2):244-51. [PubMed: 17623803]  [MGI Ref ID J:127218]

Dempsey EE; Trasler DG. 1983. Early morphological abnormalities in splotch mouse embryos and predisposition to gene- and retinoic acid-induced neural tube defects. Teratology 28(3):461-72. [PubMed: 6665745]  [MGI Ref ID J:114747]

Deol MS. 1966. Influence of the neural tube on the differentiation of the inner ear in the mammalian embryo. Nature 209(5019):219-20. [PubMed: 5912439]  [MGI Ref ID J:114748]

Epstein DJ; Vogan KJ; Trasler DG; Gros P. 1993. A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant. Proc Natl Acad Sci U S A 90(2):532-6. [PubMed: 8421686]  [MGI Ref ID J:3731]

Epstein JA; Li J; Lang D; Chen F; Brown CB; Jin F; Lu MM; Thomas M; Liu E; Wessels A; Lo CW. 2000. Migration of cardiac neural crest cells in Splotch embryos. Development 127(9):1869-78. [PubMed: 10751175]  [MGI Ref ID J:61431]

Epstein JA; Shapiro DN; Cheng J; Lam PY; Maas RL. 1996. Pax3 modulates expression of the c-Met receptor during limb muscle development. Proc Natl Acad Sci U S A 93(9):4213-8. [PubMed: 8633043]  [MGI Ref ID J:32900]

Ernest S; Christensen B; Gilfix BM; Mamer OA; Hosack A; Rodier M; Colmenares C; McGrath J; Bale A; Balling R; Sankoff D; Rosenblatt DS; Nadeau JH. 2002. Genetic and molecular control of folate-homocysteine metabolism in mutant mice. Mamm Genome 13(5):259-67. [PubMed: 12016514]  [MGI Ref ID J:76559]

Goulding M; Lumsden A; Paquette AJ. 1994. Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. Development 120(4):957-71. [PubMed: 7600971]  [MGI Ref ID J:18227]

Goulding M; Sterrer S; Fleming J; Balling R; Nadeau J; Moore KJ; Brown SD; Steel KP; Gruss P. 1993. Analysis of the Pax-3 gene in the mouse mutant splotch. Genomics 17(2):355-63. [PubMed: 8406486]  [MGI Ref ID J:13559]

Grifone R; Demignon J; Giordani J; Niro C; Souil E; Bertin F; Laclef C; Xu PX; Maire P. 2007. Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo. Dev Biol 302(2):602-16. [PubMed: 17098221]  [MGI Ref ID J:119948]

Helmbacher F; Dessaud E; Arber S; deLapeyriere O; Henderson CE; Klein R; Maina F. 2003. Met signaling is required for recruitment of motor neurons to PEA3-positive motor pools. Neuron 39(5):767-77. [PubMed: 12948444]  [MGI Ref ID J:85300]

Hill AL; Phelan SA; Loeken MR. 1998. Reduced expression of pax-3 is associated with overexpression of cdc46 in the mouse embryo. Dev Genes Evol 208(3):128-34. [PubMed: 9601985]  [MGI Ref ID J:48291]

Hornyak TJ; Hayes DJ; Chiu L; Ziff EB. 2001. Transcription factors in melanocyte development: distinct roles for Pax-3 and Mitf. Mech Dev 101(1-2):47-59. [PubMed: 11231058]  [MGI Ref ID J:68168]

Houzelstein D; Cheraud Y; Auda-Boucher G; Fontaine-Perus J; Robert B. 2000. The expression of the homeobox gene Msx1 reveals two populations of dermal progenitor cells originating from the somites. Development 127(10):2155-64. [PubMed: 10769239]  [MGI Ref ID J:61521]

Kapron-Bras CM; Trasler DG. 1984. Gene-teratogen interaction and its morphological basis in retinoic acid-induced mouse spina bifida. Teratology 30(1):143-50. [PubMed: 6385329]  [MGI Ref ID J:114749]

Kapron-Bras CM; Trasler DG. 1985. Reduction in the frequency of neural tube defects in splotch mice by retinoic acid. Teratology 32(1):87-92. [PubMed: 3898457]  [MGI Ref ID J:8010]

Kassar-Duchossoy L; Giacone E; Gayraud-Morel B; Jory A; Gomes D; Tajbakhsh S. 2005. Pax3/Pax7 mark a novel population of primitive myogenic cells during development. Genes Dev 19(12):1426-31. [PubMed: 15964993]  [MGI Ref ID J:98918]

Kochilas LK; Li J; Jin F; Buck CA; Epstein JA. 1999. p57Kip2 expression is enhanced during mid-cardiac murine development and is restricted to trabecular myocardium. Pediatr Res 45(5 Pt 1):635-42. [PubMed: 10231856]  [MGI Ref ID J:96055]

Konyukhov BV; Mironova OV. 1979. Interaction of the mutant genes splotch and fidget in mice. Sov Genet 15:407-411.  [MGI Ref ID J:11996]

Kwang SJ; Brugger SM; Lazik A; Merrill AE; Wu LY; Liu YH; Ishii M; Sangiorgi FO; Rauchman M; Sucov HM; Maas RL; Maxson RE Jr. 2002. Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest. Development 129(2):527-38. [PubMed: 11807043]  [MGI Ref ID J:73781]

Lakkis MM; Golden JA; O'Shea KS; Epstein JA. 1999. Neurofibromin deficiency in mice causes exencephaly and is a modifier for Splotch neural tube defects. Dev Biol 212(1):80-92. [PubMed: 10419687]  [MGI Ref ID J:56680]

Li D; Pickell L; Liu Y; Rozen R. 2006. Impact of methylenetetrahydrofolate reductase deficiency and low dietary folate on the development of neural tube defects in splotch mice. Birth Defects Res A Clin Mol Teratol 76(1):55-9. [PubMed: 16397891]  [MGI Ref ID J:112763]

Li J; Liu KC; Jin F; Lu MM; Epstein JA. 1999. Transgenic rescue of congenital heart disease and spina bifida in Splotch mice. Development 126(11):2495-503. [PubMed: 10226008]  [MGI Ref ID J:52760]

Machado AF; Zimmerman EF; Hovland DN Jr; Weiss R; Collins MD. 2001. Diabetic embryopathy in C57BL/6J mice. Altered fetal sex ratio and impact of the splotch allele. Diabetes 50(5):1193-9. [PubMed: 11334426]  [MGI Ref ID J:69040]

Martin LJ; Machado AF; Loza MA; Mao GE; Lee GS; Hovland DN Jr; Cantor RM; Collins MD. 2003. Effect of arsenite, maternal age, and embryonic sex on spina bifida, exencephaly, and resorption rates in the splotch mouse. Birth Defects Res Part A Clin Mol Teratol 67(4):231-9. [PubMed: 12854658]  [MGI Ref ID J:85062]

Mennerich D; Schafer K; Braun T. 1998. Pax-3 is necessary but not sufficient for lbx1 expression in myogenic precursor cells of the limb. Mech Dev 73(2):147-58. [PubMed: 9622616]  [MGI Ref ID J:48130]

Moase CE; Trasler DG. 1990. Delayed neural crest cell emigration from Sp and Spd mouse neural tube explants. Teratology 42(2):171-82. [PubMed: 2218944]  [MGI Ref ID J:114750]

Moase CE; Trasler DG. 1987. Retinoic acid-induced selective mortality of splotch-delayed mouse neural tube defect mutants. Teratology 36(3):335-43. [PubMed: 3424222]  [MGI Ref ID J:70477]

Moase CE; Trasler DG. 1989. Spinal ganglia reduction in the splotch-delayed mouse neural tube defect mutant. Teratology 40(1):67-75. [PubMed: 2763211]  [MGI Ref ID J:70476]

Morris GL; O'Shea KS. 1983. Anomalies of neuroepithelial cell associations in the Splotch mutant embryo. Brain Res 285(3):408-10. [PubMed: 6627032]  [MGI Ref ID J:70478]

Nakazaki H; Reddy AC; Mania-Farnell BL; Shen YW; Ichi S; McCabe C; George D; McLone DG; Tomita T; Mayanil CS. 2008. Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development. Dev Biol 316(2):510-23. [PubMed: 18308300]  [MGI Ref ID J:135651]

Neale SA; Trasler DG. 1994. Early sialylation on N-CAM in splotch neural tube defect mouse embryos. Teratology 50(2):118-24. [PubMed: 7801299]  [MGI Ref ID J:19959]

Oda K; Yamazaki K; Miura H; Shibasaki H; Kikuchi T. 1992. Dying back type axonal degeneration of sensory nerve terminals in muscle spindles of the gracile axonal dystrophy (GAD) mutant mouse. Neuropathol Appl Neurobiol 18(3):265-81. [PubMed: 1630580]  [MGI Ref ID J:1724]

Pani L; Horal M; Loeken MR. 2002. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis. Genes Dev 16(6):676-80. [PubMed: 11914272]  [MGI Ref ID J:75569]

Phelan SA; Ito M; Loeken MR. 1997. Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes 46(7):1189-97. [PubMed: 9200655]  [MGI Ref ID J:41232]

Relaix F; Polimeni M; Rocancourt D; Ponzetto C; Schafer BW; Buckingham M. 2003. The transcriptional activator PAX3-FKHR rescues the defects of Pax3 mutant mice but induces a myogenic gain-of-function phenotype with ligand-independent activation of Met signaling in vivo. Genes Dev 17(23):2950-65. [PubMed: 14665670]  [MGI Ref ID J:86911]

Relaix F; Rocancourt D; Mansouri A; Buckingham M. 2004. Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes Dev 18(9):1088-105. [PubMed: 15132998]  [MGI Ref ID J:90568]

Russell WL. 1947. Splotch, a new mutation in the house mouse, Mus musculus. Genetics 32:102.  [MGI Ref ID J:12957]

Schubert FR; Tremblay P; Mansouri A; Faisst AM; Kammandel B; Lumsden A; Gruss P; Dietrich S. 2001. Early mesodermal phenotypes in splotch suggest a role for Pax3 in the formation of epithelial somites. Dev Dyn 222(3):506-21. [PubMed: 11747084]  [MGI Ref ID J:72525]

Serbedzija GN; McMahon AP. 1997. Analysis of neural crest cell migration in Splotch mice using a neural crest-specific LacZ reporter. Dev Biol 185(2):139-47. [PubMed: 9187079]  [MGI Ref ID J:40428]

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Stottmann RW; Berrong M; Matta K; Choi M; Klingensmith J. 2006. The BMP antagonist Noggin promotes cranial and spinal neurulation by distinct mechanisms. Dev Biol 295(2):647-63. [PubMed: 16712836]  [MGI Ref ID J:110617]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Colony Maintenance

Mating System	Heterozygote x C57BL/6J (000664)         (Female x Male)
	C57BL/6J (000664) x Heterozygote         (Female x Male)

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

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	Usually shipped between four and eight weeks of age. This strain is included in the Neural Tube Defect Resource collection.
Request Form	Strain from the Neural Tube Defect Resource. First time use requires submission of a Request Form, please inquire.

Control Information

	Control
	Wild-type from the colony
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.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, 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 The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials 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 The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory 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 The Jackson Laboratory, 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 The Jackson Laboratory, 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 services by The Jackson Laboratory.