Phenotypes associated with this allele

• Allele Symbol: Sp3^tm1Sus
• Allele Name: targeted mutation 1, Guntram Suske
• Allele ID: MGI:2182438
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sp3^tm1Sus/Sp3^tm1Sus	involves: 129P2/OlaHsd * C57BL/6	MGI:2662384
ht2	Sp3^tm1Sus/Sp3^+	involves: 129P2/OlaHsd * C57BL/6	MGI:2662383
cx3	Sp1^tm1Phi/Sp1^+ Sp3^tm1Sus/Sp3^+	involves: 129P2/OlaHsd * C57BL/6	MGI:3809034

Genotype
MGI:2662384

hm1

• Allelic Composition: Sp3^tm1Sus/Sp3^tm1Sus
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

neonatal lethality, complete penetrance ( J:60658 )

• animals die shortly after birth due to respiratory failure despite obvious efforts to breathe

craniofacial

abnormal cranium morphology ( J:70829 )

• E18.5 homozygous mutant embryos obtained by Caesarean section occasionally display slight deformations of the skull

• notably, several mutant embryos exhibit a swelling at the roof of the skull

abnormal sagittal suture morphology ( J:70829 )

• at E18.5, homozygotes exhibit an open wide saggital suture

abnormal basicranium morphology ( J:70829 )

• impaired ossification of several bones of the skull base at E18.5

abnormal basisphenoid bone morphology ( J:70829 )

• at E18.5, the basisphenoid bone is not closed

abnormal frontal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal interparietal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal supraoccipital bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal parietal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal presphenoid bone morphology ( J:70829 )

• complete absence of an ossification centre at E18.5

abnormal tooth development ( J:60658 )

• severe defect in late tooth formation

abnormal dentin development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal enamel development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal ameloblast morphology ( J:60658 )

• no ameloblast -specific transcripts were detectable in mutant mice suggesting abnormal function

abnormal nasal bone morphology ( J:70829 )

• incomplete ossification at E18.5

growth/size/body

abnormal tooth development ( J:60658 )

• severe defect in late tooth formation

abnormal dentin development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal enamel development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal ameloblast morphology ( J:60658 )

• no ameloblast -specific transcripts were detectable in mutant mice suggesting abnormal function

abnormal nasal bone morphology ( J:70829 )

• incomplete ossification at E18.5

decreased birth body size ( J:60658 )

• at birth, homozygous animals are 25% smaller than controls

hematopoietic system

small thymus ( J:84837 )

• at E18.5, mutant thymi had approximately 30% of the cell numbers compared to controls

abnormal erythropoiesis ( J:84837 )

• delayed definitive erythropoiesis was noted in mutant embryos

abnormal B cell differentiation ( J:84837 )

• mutant mice had 2-fold less IgM^- B cells and 5-fold less IgM⁺ B cells at E18.5

decreased CD4-positive, alpha-beta T cell number ( J:84837 )

• the number of CD4⁺ and CD4⁺/CD8⁺ cells were reduced compared to controls

immune system

small thymus ( J:84837 )

• at E18.5, mutant thymi had approximately 30% of the cell numbers compared to controls

abnormal B cell differentiation ( J:84837 )

• mutant mice had 2-fold less IgM^- B cells and 5-fold less IgM⁺ B cells at E18.5

decreased CD4-positive, alpha-beta T cell number ( J:84837 )

• the number of CD4⁺ and CD4⁺/CD8⁺ cells were reduced compared to controls

liver/biliary system

liver hypoplasia ( J:84837 )

• livers were smaller in size and in total cellularity

respiratory system

abnormal nasal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal pulmonary alveolus morphology ( J:60658 )

• animals exhibit a smaller mean alveolar space diameter and thicker septa; cells comprising the alveoli are abnormal with disruption of the apical membrane

respiratory failure ( J:60658 )

• animals do not breathe and the alveoli of the lungs never fill with air

skeleton

abnormal osteoblast differentiation ( J:70829 )

• in vitro, only 15% of differentiated mutant embryonic bodies (EBs) contain mineralization nodules versus 60% in wild-type and heterozygous EBs

• expression of osteocalcin is strongly reduced in differentiated mutant EBs, indicating a reduced capacity to undergo osteoblast differentiation

abnormal cranium morphology ( J:70829 )

• E18.5 homozygous mutant embryos obtained by Caesarean section occasionally display slight deformations of the skull

• notably, several mutant embryos exhibit a swelling at the roof of the skull

abnormal sagittal suture morphology ( J:70829 )

• at E18.5, homozygotes exhibit an open wide saggital suture

abnormal basicranium morphology ( J:70829 )

• impaired ossification of several bones of the skull base at E18.5

abnormal basisphenoid bone morphology ( J:70829 )

• at E18.5, the basisphenoid bone is not closed

abnormal frontal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal interparietal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal supraoccipital bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal parietal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal presphenoid bone morphology ( J:70829 )

• complete absence of an ossification centre at E18.5

abnormal tooth development ( J:60658 )

• severe defect in late tooth formation

abnormal dentin development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal enamel development ( J:60658 )

• the dentin/enamel layer does not differentiate

abnormal ameloblast morphology ( J:60658 )

• no ameloblast -specific transcripts were detectable in mutant mice suggesting abnormal function

abnormal nasal bone morphology ( J:70829 )

• incomplete ossification at E18.5

abnormal phalanx morphology ( J:70829 )

• complete absence of ossification centres in both the distal and proximal phalanges of fore paws and hind paws at E18.5

abnormal metacarpal bone morphology ( J:70829 )

• shorter primary ossification centres in the metacarpal bones of the fore and hind paws at E18.5

abnormal metatarsal bone morphology ( J:70829 )

• shorter primary ossification centres in the metatarsal bones of the fore and hind paws at E18.5

abnormal xiphoid process morphology ( J:70829 )

• complete absence of any ossification centre in the xiphoid process at E18.5

abnormal cervical atlas morphology ( J:70829 )

• hypo-ossification of the atlas dens at E18.5

abnormal vertebral body morphology ( J:70829 )

• hypo-ossification of the vertebral bodies in the trunk region at E18.5

abnormal bone mineralization ( J:70829 )

• at E18.5, homozygotes exhibit only incomplete formation of mineralized bone tissue and expression of the osteoblast-specific protein osteocalcin is strongly reduced

abnormal sternum ossification ( J:70829 )

• hypo-ossification of the sternebrae at E18.5

delayed bone ossification ( J:70829 )

• at E18.5, homozygotes display several ossification defects during late bone development

• in contrast, cartilage formation appears to be unaffected

delayed endochondral bone ossification ( J:70829 )

• at E18.5, homozygotes display delayed ossification of the sternebrae, xiphoid process and the vertebral body

delayed intramembranous bone ossification ( J:70829 )

• at E18.5, homozygotes show delayed ossification of different skull bones including the parietal, frontal, interparietal, nasal and supraoccipital bones

limbs/digits/tail

abnormal phalanx morphology ( J:70829 )

• complete absence of ossification centres in both the distal and proximal phalanges of fore paws and hind paws at E18.5

abnormal metacarpal bone morphology ( J:70829 )

• shorter primary ossification centres in the metacarpal bones of the fore and hind paws at E18.5

abnormal metatarsal bone morphology ( J:70829 )

• shorter primary ossification centres in the metatarsal bones of the fore and hind paws at E18.5

embryo

decreased spongiotrophoblast cell number ( J:123073 )

• at E16.5, spongiotrophoblast cells are reduced

decreased spongiotrophoblast size ( J:123073 )

• at E16.5, 50% of mutant placentae show a reduced spongiotrophoblast layer

abnormal trophoblast glycogen cell morphology ( J:123073 )

• at E16.5, glycogen cells are reduced

abnormal placenta labyrinth morphology ( J:123073 )

• at E16.5, the placentas labyrinth layers appear disorganized, showing clustered streaks with small nucleated cells

• at this stage, maternal blood spaces are enlarged and disorganized, and syncytiotrophoblast cells appear stronly reduced

• although disorganized, fetal endothelial cells, pericytes, and sinusoidal trophoblast giant cells are all present

cellular

abnormal osteoblast differentiation ( J:70829 )

• in vitro, only 15% of differentiated mutant embryonic bodies (EBs) contain mineralization nodules versus 60% in wild-type and heterozygous EBs

• expression of osteocalcin is strongly reduced in differentiated mutant EBs, indicating a reduced capacity to undergo osteoblast differentiation

endocrine/exocrine glands

small thymus ( J:84837 )

• at E18.5, mutant thymi had approximately 30% of the cell numbers compared to controls

Genotype
MGI:2662383

ht2

• Allelic Composition: Sp3^tm1Sus/Sp3⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

growth/size/body

decreased body size ( J:123073 )

• heterozygotes are fertile and apparently normal, though slightly smaller than wild-type mice

hematopoietic system

abnormal erythroid progenitor cell morphology ( J:123073 )

• at E14.5, the frequency of megakaryocyte CFU-MK precursors is slightly reduced in heterozygous fetal liver cultures, while the number of BFU-Es and CFU-Es remain similar to those in wild-type liver cultures

• however, neither a reduction of enucleated red blood cells nor an increased number of nucleated primitive erythrocytes is noted in vivo at E16.5

Genotype
MGI:3809034

cx3

• Allelic Composition: Sp1^tm1Phi/Sp1⁺; Sp3^tm1Sus/Sp3⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

mortality/aging

lethality at weaning, complete penetrance ( J:123073 )

• no double heterozygotes are obtained at weaning

lethality throughout fetal growth and development, incomplete penetrance ( J:123073 )

• most double heterozygous embryos die between E16.5 and E18.5

• at E18.5, 20% of embryos are doubly heterozygous, but only one-third of them (6.7%) are alive and appear similar to Sp3^tm1Sus homozygous mutants

• at E18.5, dead embryos exhibit a swollen body shape and a diffuse pink color (41.7%), or different stages of resorption (25%)

respiratory system

abnormal lung morphology ( J:123073 )

• at E18.5, the overall tissue structure of mutant lung tissue is more compact than that of wild-type lung tissue

skeleton

abnormal cranium morphology ( J:123073 )

• at E18.5, various cranial bones are malformed

• unlike Sp3^tm1Sus homozygotes, double heterozygotes do not display a delay in the formation of the ameloblast layer of developing teeth at E18.5

abnormal phalanx morphology ( J:123073 )

• at E18.5, forelimb phalanges are malformed

abnormal bone ossification ( J:123073 )

• at E18.5, ossification in the main skull bones is incomplete and ossification centers of the paws are reduced

craniofacial

abnormal cranium morphology ( J:123073 )

• at E18.5, various cranial bones are malformed

• unlike Sp3^tm1Sus homozygotes, double heterozygotes do not display a delay in the formation of the ameloblast layer of developing teeth at E18.5

limbs/digits/tail

abnormal phalanx morphology ( J:123073 )

• at E18.5, forelimb phalanges are malformed

vision/eye

anophthalmia ( J:123073 )

• at E18.5, several viable embryos are missing one or both eyes

growth/size/body

decreased body size ( J:123073 )

• viable double heterozygous embryos are smaller than wild-type embryos

decreased fetal weight ( J:123073 )

• at E14.5, mutant body weight is only slightly reduced, but at E16.5 it is reduced to 67% of wild-type weight

• at these stages, the relative weight of mutant fetal livers and placentas, but not of other organs, is significantly reduced

hematopoietic system

abnormal erythropoiesis ( J:123073 )

• at E16.5, blood smears of peripheral blood indicate that up to 34% of mutant erythrocytes are nucleated (primitive, yolk sac-derived) relative to only about 1% in wild-type blood

• defects in erythroid development are already present at earlier stages

anemia ( J:123073 )

• at E16.5, a 4-fold reduction of enucleated red blood cells indicates anemia

• anemia is associated with impaired maturation of erythrocytes

decreased erythroid progenitor cell number ( J:123073 )

• at E14.5, the frequency of erythroid BFU-E and CFU-E precursors as well as megakaryocyte CFU-MK precursors is markedly reduced in mutant fetal liver cultures

homeostasis/metabolism

skin edema ( J:123073 )

• at E18.5, viable double heterozygotes show characteristic blood-filled distensions (edemas) on their back

• at E14.5 and E16.5, ~50% of double heterozygous embryos develop edemas along their back

liver/biliary system

abnormal liver sinusoid morphology ( J:123073 )

• at E16.5, mutant fetal liver sinusoids are virtually empty and erythrocytes are only found in the blood vessels

small liver ( J:123073 )

• mutant fetal livers are barely visible (E16.5) or smaller (E14.5) than the wild-type livers

decreased liver weight ( J:123073 )

• at E14.5 and E16.5, the relative weight of mutant fetal livers is significantly reduced

embryo

abnormal placenta morphology ( J:123073 )

• at E14.5 and E16.5, 75% of mutant placentae show a striking reversal of the curvature

decreased spongiotrophoblast cell number ( J:123073 )

• at E16.5, spongiotrophoblast cells are reduced

decreased spongiotrophoblast size ( J:123073 )

• at E14.5 and E16.5, the size of the spongiotrophoblast layer is visibly decreased

• at E16.5, trophoblast cell type marker analyses indicate that the spongiotrophoblast layer is thinner and abnormally shaped in 100% of mutant placentae

decreased trophoblast glycogen cell number ( J:123073 )

• at E16.5, trophoblast glycogen cells are reduced

abnormal placenta intervillous maternal lacunae morphology ( J:123073 )

• at E16.5, maternal blood spaces are enlarged and disorganized

disorganized placental labyrinth ( J:123073 )

• at E14.4, large portions of the labyrinth layer appear disorganized

• at E16.5, three of 4 labyrinth layers appear highly disorganized, showing clustered streaks with small nucleated cells

• although disorganized, fetal endothelial cells, pericytes, and sinusoidal trophoblast giant cells are all present

decreased placenta weight ( J:123073 )

• at E14.5 and E16.5, the relative weight of mutant placentas is only ~60% of wild-type placentas

cardiovascular system

abnormal liver sinusoid morphology ( J:123073 )

• at E16.5, mutant fetal liver sinusoids are virtually empty and erythrocytes are only found in the blood vessels

hypovolemia ( J:123073 )

• at E16.5, blood volume is significantly decreased

integument

skin edema ( J:123073 )

• at E18.5, viable double heterozygotes show characteristic blood-filled distensions (edemas) on their back

• at E14.5 and E16.5, ~50% of double heterozygous embryos develop edemas along their back

pallor ( J:123073 )

• at E14.5 amd E16.5, double heterozygotes display a pale body color