Overview

Also Known As:oligosyndactylism

Mice carrying the radiation-induced oligosyndactyly (Os) mutation on a C57BL/6 genetic background exhibit hyperlipidemia, but do not develop glomerulosclerosis as do mice carrying Os on the ROP/GnLe strain.

Genetic overview

Genetic Background	Generation

Os

Allele Type	Gene Symbol	Gene Name
Radiation induced	Os	oligosyndactylism

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Research Applications

Developmental Biology Research
Internal/Organ Research

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Base Price

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$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice carrying the radiation-induced oligosyndactyly (Os) mutation on a C57BL/6 genetic background exhibit hyperlipidemia , but do not develop glomerulosclerosis as do mice carrying Os on the ROP/GnLe strain (Stock No. 000267). Nephron number is decreased by 50% in both B6 Os/+ and ROP Os/+ mice, and a glomerular volume and labeling index are two- to threefold increased in both. Chow-fed B6.ROP Os/+ animals demonstrate glomerular hypertrophy with an increase in mesangial matrix and cellularity that is characterized by macrophage influx and increased proliferation. Hyperlipidemia in B6.ROP Os/+ mice results in increased plasma BUN compared to chow-fed B6.ROP Os/+ animals and aggravated renal pathology by further increasing glomerular matrix and glomerular hypercellularity. Glomerular transforming growth factor-beta (TGF-beta) mRNA expression is increased in B6.ROP Os/+ mice compared to controls.

Development

The Os mutation was transferred from mice of strain ROP/Le onto the C57BL/6J background by repeated backcrossing reaching N27 in 2005.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

He C; Esposito C; Phillips C; Zalups RK; Henderson DA; Striker GE; Striker LJ. 1996. Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number. J Clin Invest 97(5):1242-9PubMed: 8636436 MGI: J:32764

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Genetics

Os

Allele Symbol: Os

Allele Name	Os
Allele Type	Radiation induced
Allele Synonym(s)
Gene Symbol and Name	Os, oligosyndactylism
Gene Synonym(s)
Strain of Origin	(101 x C3H)F1
Chromosome	8
General Note	Heterozygotes are affected on all four feet. Fusion usually occurs between the second and third digits and occasionally involves the fourth (J:13049). The muscles of the forearms and lower legs as well as of the feet show anomalous arrangements not necessarily correlated with the skeletal changes (J:12944). At 11 days of gestation the preaxial border of the limbs can be seen to be reduced (J:12942), and a histological examination at this time shows that there is a small amount of cellular degeneration in the preaxial part of the footplate mesoderm, leading to coalescence of the second and third digital rudiments (J:5107). Os /+ mice have a mild diabetes insipidus present at 5 weeks and increasing with age. In combination with one or more recessive modifying genes in the selected DI stock, Os/+ mice have a severe diabetes insipidus (J:12948). The cause of the diabetes is a 45% reduction in size of the kidneys with an 80% reduction in number of glomeruli. Compensatory hypertrophy of the nephrons is not sufficient to restore normal urine-concentrating ability (J:5127)(J:5128).
Molecular Note	The oligosyndactylism mutation is due to a chromosomal inversion that has breakpoints approximately 10 Mb apart. One breakpoint appears to reside in the Anapc10 gene, and an aberrant transcript consisting of part of Anapc10 and an unrelated sequence is expressed at low levels.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Os related

Developmental Biology Research
- Skeletal Defects
  - Oligodactyly
Internal/Organ Research
- Kidney Defects
  - diabetes insipidus

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Os/Os⁺
involves: 101 * C3H

embryo phenotype

abnormal limb bud morphology
- although normal at early embryonic day 11, by embryonic day 11 to 12 there are cytolytic changes, cellular degeneration, in the preaxial part of the footplate mesoderm, leading to coalescence of the second and third digital rudiments
- retardation of the mesodermal growth in the preaxial area of the footplate of the forelimb buds is found at embryonic day 10 hour 16 and in the hindlimb buds at embryonic day 10 hour 21

limbs/digits/tail phenotype

abnormal limb bud morphology
- although normal at early embryonic day 11, by embryonic day 11 to 12 there are cytolytic changes, cellular degeneration, in the preaxial part of the footplate mesoderm, leading to coalescence of the second and third digital rudiments
- retardation of the mesodermal growth in the preaxial area of the footplate of the forelimb buds is found at embryonic day 10 hour 16 and in the hindlimb buds at embryonic day 10 hour 21

Genotype: Os/Os⁺
involves: 101 * C3H * CBA/Gr

embryo phenotype

abnormal embryonic tissue morphology
- at E14 projections of digits 2 and 3 at the edge of the foot plate are closer together than wildtype and there is only a single basal phalanx common to both digits
- at E14-5 cuneiforme 3 and cuboideum have fused to a single element and are elongated in a diagonal direction rather than circular
- at E16 metacarpalia 4 and 5 are fused

abnormal limb mesenchyme morphology
- a reduction in the amount of mesenchyme in the preaxial area of the foot plate is observed by E13

mortality/aging

prenatal lethality

skeleton phenotype

abnormal calcaneum morphology
- calcaneus frequently lacks process trochlearis

abnormal carpal bone morphology
- metacarpal 5 is in a fixed state of abduction
- ulnar end of the hamatum articulates with metacarpal 4, but does not reach metacarpal 5

abnormal navicular morphology
- naviculare is narrow as compared to wildtype

abnormal tarsal bone morphology
- long axis of calcaneus and metararsalia are not parallel, as a result hindfeet point outward

fused carpal bones
- extensive fusions in carpus

fused tarsal bones
- extensive and varied fusions in tarsus, which includes a solid fusion between talus and calcaneus
- fusion occurs between the naviculare and a composite of cuneiforme 3 and cuboideum in all animals

limbs/digits/tail phenotype

abnormal calcaneum morphology
- calcaneus frequently lacks process trochlearis

abnormal carpal bone morphology
- metacarpal 5 is in a fixed state of abduction
- ulnar end of the hamatum articulates with metacarpal 4, but does not reach metacarpal 5

abnormal embryonic autopod plate morphology
- beginning at E11 the preaxial border of the foot plate is flattened, displaying an ovoid rather than circular outline
- blastemata are crowded and small
- in most cases, digit 2 is formed closer to and may fuse to digit 3
- interdigital area between digits 2 and 3 is reduced by E13

abnormal limb mesenchyme morphology
- a reduction in the amount of mesenchyme in the preaxial area of the foot plate is observed by E13

abnormal navicular morphology
- naviculare is narrow as compared to wildtype

abnormal tarsal bone morphology
- long axis of calcaneus and metararsalia are not parallel, as a result hindfeet point outward

fused carpal bones
- extensive fusions in carpus

fused tarsal bones
- extensive and varied fusions in tarsus, which includes a solid fusion between talus and calcaneus
- fusion occurs between the naviculare and a composite of cuneiforme 3 and cuboideum in all animals

oligodactyly
- different digits in the same foot can be both polydactylous and oligodactylous
- digit loss arises by fusion of digits 2 and 3, however, digit 2 is often thinner than normal and may vanish without fusion to digit 3
- digits 2 and 3 are typically involved

polydactyly
- different digits in the same foot can be both polydactylous and oligodactylous
- exhibited in the hindfeet of some animals

polysyndactyly
- exhibited in some animals

syndactyly
- all four feet are affected, although the forefeet are less severely affected than the hindfeet
- all fusions between metacarpal and metatarsals are secondary
- hard tissue fusions start at the basal phalanges and spread distally
- in the tarsus, only the cuneiforme 3 and cuboideum fusion is primary
- most fusions are secondary, only a few of the fusions are primary hard tissue in both embryo and adult
- nearly all animals exhibit osseous fusions of the bases of metacarpalia or metatarsalia 4 and 5
- some animals exhibit fusion of metatarsalia 1 and 2
- syndactylism primarily involves digits 2 and 3

Genotype: Os/Os⁺
ROP/GnLeJ

homeostasis/metabolism phenotype

increased blood urea nitrogen level
- BUN levels are increased by almost 50% in both heterozyote and nephrectomized heterozygotes as compared to controls

immune system phenotype

glomerulonephritis
- glomerular cross-sectional area in females assessed at 3 months of age is increased by 1.8 fold compared with controls, although the fraction of the cortex occupied by glomeruli remains the same between mutant and control

renal/urinary system phenotype

abnormal kidney collecting duct principal cell morphology
- the principal cell type in the collecting duct is hypertrophied, with the greatest degree of hypertrophy in the nephrectomized heterozygotes

abnormal kidney morphology
- renal mass is reduced by 38% in comparison to wild-type

abnormal nephron morphology
- hypertrophied nephrons in females at 3 months of age

abnormal proximal convoluted tubule morphology
- segments of proximal tubule, especially pars recta, exhibit hypertrophy

abnormal renal glomerulus morphology
- bone marrow transplant from heterozygotes into wild-type coisognic hosts results in mesangial sclerosis and glomerular hypertrophy
- in females at 3 weeks of age there is a 34% increase in mean cell number per glomerulus compared with controls
- size of glomeruli is slightly increased in left kidney following unilateral nephrectomy as compared to control
- Background Sensitivity - this mutation on a C57BL/6J background does not show significant glomerular histopathology

decreased compensatory renal growth
- in nephrectomized heterozygote males, compensatory kidney growth is reduced in comparison to controls

decreased kidney weight
- females at 3 months of age have a 24% reduction in kidney weight but no concomitant change in body or heart weight

decreased renal glomerulus number
- females assessed at 3 months of age have a 55% reduction in the mean glomerular number per kidney
- midtranverse sections from the left kidney indicate that glomeruli density is reduced by 50% in heterozygotes

expanded mesangial matrix
- in females at 3 months of age mesangial sclerosis affects all glomeruli and is evenly distributed in the cortical and justaglomerular regions, with increased extracellular matrix including type IV collagen and tenascin, but no inflammatory cells are found

glomerulonephritis
- glomerular cross-sectional area in females assessed at 3 months of age is increased by 1.8 fold compared with controls, although the fraction of the cortex occupied by glomeruli remains the same between mutant and control

glomerulosclerosis
- Background Sensitivity - on the ROP background but not the C57BL/6J background at 5 months of age there is severe and diffuse glomerulosclerosis restricted to the mesangial regions, with a large excess of type IV collagen and tenascin in the mesangial areas

increased urine flow rate
- Normal - excretion of creatinine, sodium and potassium is similar to control
- rate of urine flow is increased in heterozygotes as compared to controls, however glomerular filtration rate is not affected

renal tubule hypertrophy
- diameters of the proximal convoluted and straight tubules are increased in size as compared to wild-type
- tubular epithelial cells are hypertrophied in both heterozyote and nephrectomized heterozygotes, however, the magnitude of hypertrophy is increased in unaltered mice

Genotype: Os/Os
involves: 101 * C3H

cellular phenotype

abnormal mitosis

increased mitotic index
- E4.5 embryos have an index nine times that of controls
- more than one third of cells contain mitotic figures

embryo phenotype

decreased embryo size
- noted as early as E4.5

embryonic growth arrest
- cells of the developing embryo appear abnormal between the 7th and 8th division with suggestion of mitotic dysfunction
- in culture, blastocysts show rapid degeneration of the inner cell mass compared with control embryos
- the most striking abnormalities are seen by the middle of the 4th day when many embryonic cells contain fragmented, pycnotic chromatin and lack nuclear membrane and nucleolus

growth/size/body region phenotype

decreased embryo size
- noted as early as E4.5

mortality/aging

embryonic lethality between implantation and placentation, complete penetrance

The following phenotype relates to a compound genotype created using this strain

Genotype: Os/Os⁺
B6.ROP/Le-Os/J

renal/urinary system phenotype

abnormal renal glomerulus morphology
- glomerular volume is increased 2-fold relative to controls at 3 months of age and 3-fold at 5 months of age but the glomerulosclerosis found on the ROP background is absent with only a minimal increase in extracellular matrix at 5 months of age
- the mean cell number per glomerulus is increased 21% relative to controls and the glomerular labeling index is increased 2.6 fold at 3 and 5 months of age

decreased kidney weight
- 34% reduction in kidney weight compared with controls at 3 months of age

decreased renal glomerulus number
- mean glomerular number per kidney is reduced by 50% at 3 months of age

expanded mesangial matrix
- only a minimal increase in extracellular matrix is noted at 5 months of age

References

He C; Esposito C; Phillips C; Zalups RK; Henderson DA; Striker GE; Striker LJ. 1996. Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number. J Clin Invest 97(5):1242-9PubMed: 8636436 MGI: J:32764

Additional References

Pravtcheva DD; Wise TL. 1996. A transgene-induced mitotic arrest mutation in the mouse allelic with Oligosyndactylism. Genetics 144(4):1747-56PubMed: 8978060 MGI: J:38877
Pravtcheva DD; Wise TL. 2001. Disruption of Apc10/Doc1 in three alleles of oligosyndactylism. Genomics 72(1):78-87PubMed: 11247669 MGI: J:81567

Additional - Os related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Appearance
- black, fused digits
  Related Genotype: a/a Os/+
  
  black, unaffected
  Related Genotype: a/a +/+
Citation
When using the oligosyndactylism mouse strain in a publication, please cite the originating article(s) and include JAX stock #003523 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

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Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Os

Related Products and Services

Frozen Mouse Embryo	B6.ROP/Le-Os/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.ROP/Le-Os/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.ROP/Le-Os/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.ROP/Le-Os/J Frozen Embryo	$3373.50

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Also Known As:oligosyndactylism

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Os

Allele Symbol: Os

Disease Terms

Research Areas By Phenotype

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

Genotype: Os related

Mammalian Phenotype Terms by Genotype

Genotype: Os/Os+involves: 101 * C3H

embryo phenotype

limbs/digits/tail phenotype

Genotype: Os/Os+involves: 101 * C3H * CBA/Gr

embryo phenotype

mortality/aging

skeleton phenotype

limbs/digits/tail phenotype

Genotype: Os/Os+ROP/GnLeJ

homeostasis/metabolism phenotype

immune system phenotype

renal/urinary system phenotype

Genotype: Os/Osinvolves: 101 * C3H

cellular phenotype

embryo phenotype

growth/size/body region phenotype

mortality/aging

Genotype: Os/Os+B6.ROP/Le-Os/J

renal/urinary system phenotype

References

Additional References

Additional - Os related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Os/Os⁺
involves: 101 * C3H

Genotype: Os/Os⁺
involves: 101 * C3H * CBA/Gr

Genotype: Os/Os⁺
ROP/GnLeJ

Genotype: Os/Os
involves: 101 * C3H

Genotype: Os/Os⁺
B6.ROP/Le-Os/J