Pax3<Sp> Spontaneous Allele Detail MGI Mouse (MGI:1856173)

Pax3^Sp
Spontaneous Allele Detail

Nomenclature

Symbol:	Pax3^Sp
Name:	paired box gene 3; splotch
MGI ID:	MGI:1856173
Synonyms:	Sp
Gene:	Pax3 Location: Chr1:78099267-78193711 bp, - strand Genetic Position: Chr1, 44.0 cM

Pax3^Sp/+ and Kitl^Sl/+

Show the 1 image(s) involving this allele.

Mutation
origin

Strain of Origin:

C57BL

Mutation
description

Allele Type:	Spontaneous
Mutation:	Single point mutation
	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. (J:3731)
Inheritance:	Semidominant

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:	Mouse Strains: 5 strains available Cell Lines: 0 lines available
Carrying any Pax3 Mutation:	12 strains or lines available

Expression

In Mice Carrying this Mutation:

134 assay results

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems

Genotypes:

cellular

√

embryogenesis

√

hearing/vestibular/ear

√

homeostasis/metabolism

√

lethality/prenatal-perinatal

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limbs/digits/tail

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muscle

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nervous system

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pigmentation

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skeleton

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skin/coat/nails

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Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
hm1	Pax3^Sp/Pax3^Sp	BR.B-Pax3^Sp
lethality/prenatal-perinatal perinatal lethality (J:11996) Background Sensitivity: mice die later compared to mice on a mixed genetic background that includes C57BL die around E18-E19 nervous system spina bifida (J:11996) spina bifida aperta in the lumbosacral area embryogenesis spina bifida (J:11996) spina bifida aperta in the lumbosacral area
Genotype	Allelic Composition	Genetic Background
hm2	Pax3^Sp/Pax3^Sp	C57BL-Pax3^Sp
lethality/prenatal-perinatal lethality throughout fetal growth and development (J:12957) die around E14 nervous system abnormal neural tube morphology/development (J:13016, J:6190) overgrowth of neural tissue in the region of the open neural tube is variable and becomes more pronounced with age (J:13016) neural overgrowth occurs laterad from the mid-dorsal line of the neural folds (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 (J:6190) open neural tube (J:13016, J:5443) at E9.5, neural folds are open in the hindlimb region with aggregation of neural tissue on both sides of the dorsal midline (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 (J:13016) the extent of the area of open neural tube tends to increase in proportion to growth of the embryo (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 (J:13016) open neural folds in the hindbrain region (J:5443) spina bifida (J:12957) small telencephalic vesicles (J:13016) vesicles appear as a network of small channels abnormal midbrain development (J:13016, J:5443) the lumen in the mesencephalic region is greatly reduced and obscured by neural tissue (J:13016) at E10 and E11, mesencephalic ventricular cells display increased generation time, increased mitotic index, and prolonged mitosis, S phase, and G1 (J:5443) abnormal brain ventricle morphology (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 (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 limbs/digits/tail abnormal tail morphology (J:13016) distorted shape correlated to degree of rachischisis and neural overgrowth hematomas are frequently found in regions of tail curvature kinked tail (J:12957) pigmentation absent coat pigmentation (J:13016) embryonic tissue explants allowed to develop until hair is formed display well developed hairs that are devoid of pigment absent skin pigmentation (J:13016) embryonic tissue explants allowed to develop until the time when pigment would normally form are devoid of pigment skin/coat/nails absent coat pigmentation (J:13016) embryonic tissue explants allowed to develop until hair is formed display well developed hairs that are devoid of pigment absent skin pigmentation (J:13016) embryonic tissue explants allowed to develop until the time when pigment would normally form are devoid of pigment cellular increased mitotic index (J:13016) at E10 and 11, mesencephalic ventricular cells have increased mitotic index compared to wild-type embryogenesis abnormal neural tube morphology/development (J:13016, J:6190) overgrowth of neural tissue in the region of the open neural tube is variable and becomes more pronounced with age (J:13016) neural overgrowth occurs laterad from the mid-dorsal line of the neural folds (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 (J:6190) open neural tube (J:13016, J:5443) at E9.5, neural folds are open in the hindlimb region with aggregation of neural tissue on both sides of the dorsal midline (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 (J:13016) the extent of the area of open neural tube tends to increase in proportion to growth of the embryo (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 (J:13016) open neural folds in the hindbrain region (J:5443) spina bifida (J:12957)
Genotype	Allelic Composition	Genetic Background
hm3	Pax3^Sp/Pax3^Sp	involves: 129S2/SvPas * C57BL * C57BL/6J * FVB
nervous system abnormal embryonic neuroepithelium morphology (J:75569) smany apoptotic neuroepithelial cells seen at the site of the neural tube defect open neural tube (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 abnormal embryonic neuroepithelium morphology (J:75569) smany apoptotic neuroepithelial cells seen at the site of the neural tube defect open neural tube (J:75569) seen in all mice treatment with pifithrin-alpha from E8.5 to E9.5 prevented neural tube defects in 55% of embryos
Genotype	Allelic Composition	Genetic Background
hm4	Pax3^Sp/Pax3^Sp	involves: C57BL
lethality/prenatal-perinatal embryonic lethality during organogenesis (J:11996) Background Sensitivity: mice die earlier compared to homozygotes on a congenic C57BR background die around E13-E14 muscle abnormal myogenesis (J:112275, J:18227, J:32016) lack myogenic cells in the forming limb buds and hypoglossal cord at E11.5 (J:112275) at E10.5 Pax3 expressing cells are absent from the forelimb and hindlimb buds (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 (J:18227) limb buds from E11 embryos cultured for 4 days fail to generate any cells expressing early myogenic markers (desmin and sarcomeric myosin) (J:32016) however, cells from somites grafted into chick limbs are able to undergo myogenic differentiation (J:32016) abnormal muscle progenitor cell migration (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 abnormal dermomyotome development (J:112275, J:32016) foreshortening of the epaxial domain and complete loss of the hypaxial domain of the dermomyotome at E10.5 (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 (J:32016) nervous system open neural tube (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 (J:112275, J:110617) 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 (J:110617) hearing/vestibular/ear abnormal otic vesicle development (J:114748) in mice where the neural tube defect extends to the cranial region abnormal bony labyrinth (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 decreased cochlear coiling (J:114748) at E12 cochlear coiling is poor abnormal endolymphatic duct morphology (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 (J:114748) at E10, the endolymphatic duct is shorter than normal abnormal semicircular canal (J:114748) present but abnormally located in terms of their planes, point of origin, and relationship to other structures in the labyrinth abnormal saccule morphology (J:114748) difficult to distinguish and highly abnormal abnormal utricle morphology (J:114748) difficult to distinguish and highly abnormal embryogenesis open neural tube (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 (J:112275, J:110617) 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 (J:110617)
Genotype	Allelic Composition	Genetic Background
ht5	Pax3^Sp/Pax3⁺	C57BL-Pax3^Sp
pigmentation white spotting (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 (J:12957) skin/coat/nails white spotting (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 (J:12957)
Genotype	Allelic Composition	Genetic Background
ht6	Pax3^Sp/Pax3⁺	involves: C3HeB * C57BL * C57BL/6J * SWV
nervous system spina bifida (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 spina bifida (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
Genotype	Allelic Composition	Genetic Background
ht7	Pax3^Sp/Pax3⁺	involves: C57BL * C57BL/6J * CBA
hearing/vestibular/ear hearing/vestibular/ear phenotype (J:2179) auditory function and ear morphology are similar to wild-type mice
Genotype	Allelic Composition	Genetic Background
ht8	Pax3^tm1Buck/Pax3^Sp	involves: 129P2/OlaHsd * C57BL
lethality/prenatal-perinatal prenatal lethality (J:86911) stated to display the same phenotype as Pax3^Sp mice; however, no data is provided in J:86911 nervous system open neural tube (J:86911) stated to display the same phenotype as Pax3^Sp mice exencephaly (J:86911) stated to display the same phenotype as Pax3^Sp mice incidence is less than the incidence of spina bifida absent dorsal root ganglion (J:86911) muscle abnormal myogenesis (J:86911) stated to display the same phenotype as Pax3^Sp mice including absence of limb muscles at E11.5 abnormal dermomyotome development (J:86911) stated to display the same phenotype as Pax3^Sp embryogenesis open neural tube (J:86911) stated to display the same phenotype as Pax3^Sp mice abnormal neural crest cell migration (J:86911) impaired
Genotype	Allelic Composition	Genetic Background
ht9	Pax3^{tm3.1(Pax7)Buck}/Pax3^Sp	involves: 129S2/SvPas
lethality/prenatal-perinatal perinatal lethality (J:90568) perinatal lethality probably related to impaired diaphragm development is seen cellular decreased cell proliferation (J:90568) proliferation of the muscle progenitor cells is reduced about 40% compared to wild-type muscle abnormal myogenesis (J:90568) forelimb muscles and hindlimb palm muscles are absent and hindlimb muscles are reduced abnormal diaphragm morphology (J:90568) development of the diaphragm is also impaired as a result of impaired progenitor cell migration skin/coat/nails skin/coat/nails phenotype (J:90568) no melanocyte abnormalities are seen nervous system spina bifida (J:90568) failure of neural tube closure is seen at about the same rate as in Pax3^Sp heterozygotes embryogenesis spina bifida (J:90568) failure of neural tube closure is seen at about the same rate as in Pax3^Sp heterozygotes
Genotype	Allelic Composition	Genetic Background
cn10	Pax3^{tm2.1(PAX3/FOXO1A)Buck}/Pax3^Sp	involves: 129S2/SvPas * BALB/c * C57BL * C57BL/6
lethality/prenatal-perinatal prenatal lethality (J:86911) phenotype is stated to be similar to Pax3^{tm2.1(PAX3/FOXO1A)Buck} heterozygotes embryogenesis abnormal somite development (J:86911) disorganized boundaries between the hypaxial somites; however, none of the defects seen in Pax3^Sp homozygotes are present in these mice muscle abnormal muscle development (J:86911) phenotype is stated to be similar to Pax3^{tm2.1(PAX3/FOXO1A)Buck} heterozygotes skeleton abnormal rib development (J:86911) phenotype is stated to be similar to Pax3^{tm2.1(PAX3/FOXO1A)Buck} heterozygotes
Genotype	Allelic Composition	Genetic Background
cx11	Fign^fi/Fign^fi Pax3^Sp/Pax3^Sp	BR.Cg-Pax3^Sp Fign^fi
lethality/prenatal-perinatal prenatal lethality (J:11996) lethality is reduced compared to mice homozygous for the Pax3 mutation alone and similar to mice homozygous for the Fign mutation alone nervous system open neural tube (J:11996) incidence of embryos with an open neural tube is dramatically reduced compared to mice homozygous for the Pax3 mutation alone embryogenesis open neural tube (J:11996) incidence of embryos with an open neural tube is dramatically reduced compared to mice homozygous for the Pax3 mutation alone
Genotype	Allelic Composition	Genetic Background
cx12	Lbx2^tm1Fchn/Lbx2^tm1Fchn Pax3^Sp/Pax3^Sp	involves: 129S1/Sv * 129X1/SvJ * C57BL/6
nervous system open neural tube (J:121890) defects seen with Pax3 homozygosity are not affected by Lbx2-deficiency at E10.5-13.5 exencephaly (J:121890) defects seen with Pax3 homozygosity are not affected by Lbx2-deficiency at E10.5-13.5 abnormal cranial ganglia morphology (J:121890) Lbx2 expression is significantly decreased with Pax3 deficiency abnormal dorsal root ganglion morphology (J:121890) Lbx2 expression is significantly decreased with Pax3 deficiency homeostasis/metabolism edema (J:121890) defects seen with Pax3 homozygosity are not affected by Lbx2-deficiency at E10.5-13.5 embryogenesis open neural tube (J:121890) defects seen with Pax3 homozygosity are not affected by Lbx2-deficiency at E10.5-13.5
Genotype	Allelic Composition	Genetic Background
cx13	Pax3^Sp/Pax3^Sp Trp53^tm1Tyj/Trp53⁺	involves: 129S2/SvPas * C57BL * C57BL/6J * FVB
nervous system open neural tube (J:75569) incidence is reduced to 58% compared to 100% in mice homozygous for the Pax3 mutation alone embryogenesis open neural tube (J:75569) incidence is reduced to 58% compared to 100% in mice homozygous for the Pax3 mutation alone
Genotype	Allelic Composition	Genetic Background
cx14	Pax3^Sp/Pax3^Sp Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * C57BL * C57BL/6J * FVB
nervous system nervous system phenotype (J:75569) all mice have closed neural tubes and no neuroepithelial apoptosis is seen, unlike mice homozygous for the Pax3 mutation alone

References

Original:	J:120 Snell GD et al., "Linkage of loop-tail, leaden, splotch and fuzzy in the mouse" Heredity 1954;8():271-273
All:	65 reference(s)

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