Strain Detail Sheet

Strain Name    :

JU.B-Pax3Sp/Mmmh

Stock Number :

000172-MU

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Pax3Sp
Name: splotch
Chromosome: 1
Alteration at locus: Spontaneous Mutation
Gene Symbol: Pax3
Name: paired box 3
Chromosome: 1
Alteration at locus: Spontaneous Mutation

Genetic Alterations:
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. (Mouse Genome Database (MGD), Mouse Genome Informatics Web Site, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (URL: http://www.informatics.jax.org). Jan, 2004.)

Genotype Determination:

ES Cell Line: Not Applicable

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Homozygous state is embryonic lethal. Heterozygous mice have a white spot/stripe on the forehead and a large white spot on the belly.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Pax3Sp/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)
  • integument 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)
Pax3Sp/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
  • embryogenesis 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
Pax3Sp/Pax3+
        involves: C57BL * C57BL/6J * CBA
  • hearing/vestibular/ear phenotype
    • hearing/vestibular/ear phenotype (MGI Ref ID J:2179)
      • auditory function and ear morphology are similar to wild-type mice
Pax3Sp/Pax3Sp
        BR.B-Pax3<Sp>
  • mortality/aging
    • complete 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
  • embryogenesis phenotype
    • spina bifida (MGI Ref ID J:11996)
      • spina bifida aperta in the lumbosacral area
Pax3Sp/Pax3Sp
        C57BL-Pax3<Sp>
  • mortality/aging
    • complete 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 IDs J:5443, J:13016)
      • the lumen in the mesencephalic region is greatly reduced and obscured by neural tissue (MGI Ref ID J:13016)
      • at E10 and E11, mesencephalic ventricular cells display increased generation time, increased mitotic index, and prolonged mitosis, S phase, and G1 (MGI Ref ID J:5443)
    • abnormal neural tube morphology/development (MGI Ref IDs J:6190, J:13016)
      • overgrowth of neural tissue in the region of the open neural tube is variable and becomes more pronounced with age (MGI Ref ID J:13016)
      • neural overgrowth occurs laterad from the mid-dorsal line of the neural folds (MGI Ref ID J:13016)
      • 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 (MGI Ref ID J:6190)
      • open neural tube (MGI Ref IDs J:5443, 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 (MGI Ref ID J:13016)
        • 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 (MGI Ref ID J:13016)
        • the extent of the area of open neural tube tends to increase in proportion to growth of the embryo (MGI Ref ID J:13016)
        • 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 (MGI Ref ID J:13016)
        • open neural folds in the hindbrain region (MGI Ref ID J:5443)
        • 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
  • 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
  • embryogenesis phenotype
    • abnormal neural tube morphology/development (MGI Ref IDs J:6190, J:13016)
      • overgrowth of neural tissue in the region of the open neural tube is variable and becomes more pronounced with age (MGI Ref ID J:13016)
      • neural overgrowth occurs laterad from the mid-dorsal line of the neural folds (MGI Ref ID J:13016)
      • 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 (MGI Ref ID J:6190)
      • open neural tube (MGI Ref IDs J:5443, 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 (MGI Ref ID J:13016)
        • 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 (MGI Ref ID J:13016)
        • the extent of the area of open neural tube tends to increase in proportion to growth of the embryo (MGI Ref ID J:13016)
        • 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 (MGI Ref ID J:13016)
        • open neural folds in the hindbrain region (MGI Ref ID J:5443)
        • spina bifida (MGI Ref ID J:12957)
  • integument 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
Pax3Sp/Pax3Sp
        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
  • embryogenesis 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
Pax3Sp/Pax3Sp
        involves: C57BL
  • mortality/aging
    • complete 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 IDs J:32016, J:112275, J:18227)
      • lack myogenic cells in the forming limb buds and hypoglossal cord at E11.5 (MGI Ref ID J:112275)
      • at E10.5 Pax3 expressing cells are absent from the forelimb and hindlimb buds (MGI Ref ID J:18227)
      • 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 (MGI Ref ID J:18227)
      • limb buds from E11 embryos cultured for 4 days fail to generate any cells expressing early myogen ic markers (desmin and sarcomeric myosin) (MGI Ref ID J:32016)
      • however, cells from somites grafted into chick limbs are able to undergo myogenic differentiation (MGI Ref ID J:32016)
      • abnormal dermomyotome development (MGI Ref IDs J:32016, J:112275)
        • foreshortening of the epaxial domain and complete loss of the hypaxial domain of the dermomyotome at E10.5 (MGI Ref ID J:112275)
        • 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 (MGI Ref ID J:32016)
      • 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 IDs J:112275, J:110617)
        • (MGI Ref ID J:112275)
        • treatment with folate solution of heterozygous females crossed to heterozygous males results in 40% decrease in spina bifida incidence in homozygous embryos examined at midgestation (MGI Ref ID J:110617)
  • 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 development (MGI Ref ID J:114748)
      • in mice where the neural tube defect extends to the cranial region
    • abnormal semicircular canal morphology (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
    • abnormal vestibular saccule 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
  • embryogenesis 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 IDs J:112275, J:110617)
        • (MGI Ref ID J:112275)
        • treatment with folate solution of heterozygous females crossed to heterozygous males results in 40% decrease in spina bifida incidence in homozygous embryos examined at midgestation (MGI Ref ID J:110617)

Strain of Origin: C57BL/6J

Strain genetic background: JU/CtLm (MMRRC:000136)

Strain Development: The spontaneous mutation occurred in a C57BL/6 colony at the Jackson Laboratory. Starting with C57BL/6J-Pax3Sp/J, donor backcrossed to JU/CtLm more than 10 generations.

Suggested Control Mice:

Research Applications

  • Modifier genes
  • Pigmentation
  • Neural crest and neural tube defects
  • Waardenburg syndrome, type 1

Strain Origin

Donor: Dr. ML Lamoreux, Texas A&M University

Primary Reference:

  • Russell WL, Splotch, a new mutation in the house mouse, Mus musculus., Genetics 1947;32():102.
  • Epstein DJ, Vogan KJ, Trasler DG, Gros P. 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. 1993 Jan 15;90(2):532-6.(Medline PMID: 8421686)
  • Martin LJ, Machado AF, Loza MA, Mao GE, Lee GS, Hovland DN Jr, Cantor RM, Collins MD. 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. 2003 Apr;67(4):231-9. (Medline PMID: 12854658)

Colony and Husbandry Information

Special Considerations

Feed 9% fat diet.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Appearance

Coat color: Black with white spotting and prominent head spot.

Other:


Breeding

MMRRC Breeding System: Sib mating or backcross

Breeding Scheme(s):

  • Wildtype female x Heterozygous male
  • Heterozygous female x Wildtype male
  • Heterozygous female x Heterozygous male

Generation: N10+

Overall Breeding Performance: Good

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: No No
Homozygotes are fertile: No No
Heterozygotes are fertile: Yes Yes
 
Age Reproductive Decline: 52 weeks 52 weeks

Average litter size: 8

Recommended wean age: 4 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

Fees

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
000172-MU-RESUSLitter recovered from cryo-archive
$2,022.00 / $4,109.00
Non-Profit / For-Profit
Litter Recovered litter1; additional fees for any special requests.
000172-MU-SPERMCryo-preserved spermatozoa
$437.00 / $817.00
Non-Profit / For-Profit
Aliquot Approximate quantity.2
000172-MU-EMBRYOCryo-preserved embryos
$1,038.00 / $2,621.00
Non-Profit / For-Profit
Aliquot Approximate quantity3: 20-40 embryos / aliquot

1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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