JAX Mouse Strain Datasheet - 000231

B6;C3Fe a/a-Csf1^op/J

Stock No:: 000231 |; osteopetrosis

Spontaneous Mutation

Repository Live

Overview

Also Known As: osteopetrosis

Mice homozygous for the osteopetrosis spontaneous mutation (Csf1^op) may be useful to study the role of glia in neurological disease.

Genetic overview

Genetic Background	Generation
	N70 (26-NOV-14)

Csf1^op

Allele Type	Gene Symbol	Gene Name
Spontaneous	Csf1	colony stimulating factor 1 (macrophage)

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Research Applications

Internal/Organ Research
Neurobiology Research
Cancer Research
Developmental Biology Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Research Tools

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Base Price

Starting at:

$255.00 Domestic price for female

$424.90 Domestic price for breeder pair

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the osteopetrosis spontaneous mutation (Csf1^op) are viable and exhibit osteopetrosis. The osteoclasts are the primary cell type affected in homozygous mutant mice. This results in a generalized macrophage deficiency, monocytopenia, and defective bone remodeling. Homozygous mutant mice also have abnormal calcium regulation, impaired dental growth and female mice fail to lactate. Total leukocyte counts are reduced and marrow cells are decreased to one-tenth of normal control mice.Homozygous mutant mice have a deficient microglia and macrophage response, and therefore may be useful tools to study the role of glia in neurological disease if mated to transgenic models of neurodegenerative disease.

Development

The osteopetrotic mutation arose spontaneously in 1970 at The Jackson Laboratory in the beginning congenic stock that became B6.DW-Pou1f1^dw/J, which was then at generation N3. Osteopetrotic heterozygotes were backcrossed to C57BL/6J for 7 generations. The line was then bred once to C3FeLe.B6-a/a/J and the strain was subsequently maintained via homozygous ovarian transplant host bred to (C57BL/6J x C3FeLe.B6-a/a/J)F1 then intercross of the obligate heterozygous offspring.

Control Suggestions

Untyped from the colony

Additional Information

Considerations for Choosing Controls

Genetics

Csf1^op

Allele Symbol: Csf1^op

Allele Name	osteopetrosis
Allele Type	Spontaneous
Allele Synonym(s)	Csf-1^op; Csf1^- op; Csfm^op; M-; csfmop; op
Gene Symbol and Name	Csf1, colony stimulating factor 1 (macrophage)
Gene Synonym(s)	C87615; CSF-1; Csfm; Csfm; M-CSF; MCSF; colony stimulating factor, macrophage; colony-stimulating factor-1; expressed sequence C87615; op; osteopetrosis
Strain of Origin	B6;DW-Pou1f1
Chromosome	3
General Note	Phenotypic Similarity to Human Syndrome: Osteopetrosis, autosomal recessive in homozygous mice (J:26978)
Molecular Note	A single nucleotide (T) insertion 262 bp downstream from the initiation codon resulted in a frameshift and the creation of a stop codon 21 bp downstream of the insertion.

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)	AGSW; AGTI; AGTIL; ASP; As; As; SHEP9; agouti; agouti signal protein; agouti suppressor
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Phenotypic Similarity to Human Syndrome: Metabolic Syndrome in mice homozygous for Apoe^tm1Unc and heterozygous for A^y and a (J:177084)
Molecular Note	Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats. The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Internal/Organ Research
- Skeleton
  - Bone
Neurobiology Research
- Alzheimer's Disease
- Parkinson's Disease

Genotype: Csf1^op related

Cancer Research
- Growth Factors/Receptors/Cytokines
Developmental Biology Research
- Skeletal Defects
  - osteopetrosis
Endocrine Deficiency Research
- Bone/Bone Marrow Defects
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
- Immunodeficiency Associated with Other Defects
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Macrophage Deficiency

Mammalian Phenotype Terms by Genotype

Genotype: Csf1^op/Csf1^op
involves: C3HeB/FeJ * C57BL/6J

homeostasis/metabolism phenotype

abnormal circulating calcium level
- unable to raise serum calcium concentration in response to parathyroid extract (PTE)

decreased circulating phosphate level
- phosphate serum levels are low but calcium levels are normal

decreased circulating testosterone level
- mutant male mice have a seven-fold lower concentration of circulating testosterone than wild-type mice

reproductive system phenotype

abnormal ovary morphology
- very few macrophages present in ovaries at all stages of cycle and follicular development

abnormal ovulation
- significantly lower ovulation rate and frequency

abnormal proestrus
- mice do not display the characteristic surge in circulating estradiol-17 beta expected during proestrus

abnormal sperm number
- a lower then normal number of viable sperm are detected
- normal numbers of viable sperm are restored after testosterone or CSF-1 treatment throughout the postnatal period

abnormal testis physiology
- testosterone level in the tesis is lower than normal

decreased corpora lutea number

decreased fertilization frequency
- only 50% of the mated superovulated mutant females produced fertilized ooctyes compared with 83.3% of the mated superovulated heterozygous females

decreased litter size

decreased ovulation rate
- 20% of ovaries fail to undergo ovulation
- the ovulation rate is low for mice that do ovulate

impaired embryo implantation
- a lower than normal number of implantations are seen

prolonged estrous cycle
- females reach estrus every 14 days compared with a normal approximately 5 day cycle
- subcutaneous adninistration of CSF-1 from birth restores a normal estrous cycle

reduced female fertility

integument phenotype

abnormal branching of the mammary ductal tree
- precocious development of the lobulo-alveolar system

abnormal lactation
- milk proteins are expressed but parturition does not initiate lactation

abnormal mammary gland development

abnormal mammary gland growth during lactation
- incomplete mammary gland ductal growth occurs during pregnancy

abnormal mammary gland lobule morphology

cellular phenotype

abnormal osteoclast differentiation
- exogenous M-CSF enables normal osteoclast differentiation

behavior/neurological phenotype

abnormal eating behavior
- pups drink less of the mother's milk possibly due to being unable to compete with normal littermates

abnormal mating frequency
- only 64.4% of superovulated mutant females successfully mated as evidenced by a vaginal plug compared with 88.9% of mated superovulated heterozygous females

reduced male mating frequency
- normal mating behavior is restored following treatment with circulating testosterone or CSF-1 throughout the postnatal period

cardiovascular system phenotype

decreased susceptibility to atherosclerosis
- lesions are also less frequent and when present, less advanced with no lesions containing fibrous caps observed
- mice on a high fat diet for 15 weeks develop smaller atherosclerosis lesions than do the C57BL/6J controls

growth/size/body region phenotype

absent teeth
- at weaning mice need to be provided with soft food in order to thrive
- noticeably absent at 10 days of age

decreased body weight
- mice have decreased body weight until weaning when they will normalize their weight if fed a liquid diet

hematopoietic system phenotype

abnormal osteoclast cell number

abnormal osteoclast differentiation
- exogenous M-CSF enables normal osteoclast differentiation

decreased osteoclast cell number
- at birth the osteoclast population appears normal but quickly decreases to negligible numbers by the time the mouse is 3-4 days of age

immune system phenotype

abnormal osteoclast cell number

abnormal osteoclast differentiation
- exogenous M-CSF enables normal osteoclast differentiation

decreased osteoclast cell number
- at birth the osteoclast population appears normal but quickly decreases to negligible numbers by the time the mouse is 3-4 days of age

skeleton phenotype

abnormal bone marrow cavity morphology
- the excessive accumulations of bone lack marrow cavities

abnormal bone remodeling
- although bone remodeling is reduced, overall decline in rate of bone formation removes excess bone resulting in nearly normal bone
- compared with normal littermates, bone matrix formation is significantly elevated before 40 days of age and significantly reduced between 81 days and 10 months of age

abnormal osteoclast cell number

abnormal osteoclast differentiation
- exogenous M-CSF enables normal osteoclast differentiation

absent teeth
- at weaning mice need to be provided with soft food in order to thrive
- noticeably absent at 10 days of age

decreased osteoclast cell number
- at birth the osteoclast population appears normal but quickly decreases to negligible numbers by the time the mouse is 3-4 days of age

domed cranium
- mutants are recognized at 10 days of age by a characteristic domed head

craniofacial phenotype

absent teeth
- at weaning mice need to be provided with soft food in order to thrive
- noticeably absent at 10 days of age

domed cranium
- mutants are recognized at 10 days of age by a characteristic domed head

endocrine/exocrine gland phenotype

abnormal branching of the mammary ductal tree
- precocious development of the lobulo-alveolar system

abnormal lactation
- milk proteins are expressed but parturition does not initiate lactation

abnormal mammary gland development

abnormal mammary gland growth during lactation
- incomplete mammary gland ductal growth occurs during pregnancy

abnormal mammary gland lobule morphology

abnormal ovary morphology
- very few macrophages present in ovaries at all stages of cycle and follicular development

abnormal testis physiology
- testosterone level in the tesis is lower than normal

abnormal thyroid parafollicular C-cell morphology
- this cell population is increased in this mutation

decreased corpora lutea number

Genotype: Csf1^op/Csf1^op
B6;C3Fe a/a-Csf1^op/J

immune system phenotype

abnormal microglial cell morphology
- decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

decreased macrophage cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice
- numbers are significantly decreased in atral follicles
- numbers were enhanced by treatment with macrophage colony-stimulating factor

impaired macrophage chemotaxis
- to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

growth/size/body region phenotype

abnormal postnatal growth
- growth of mutants is slower than wild-type mice

cellular phenotype

impaired granulosa cell differentiation
- the numbers of cells in the atral follicles are significantly reduced but differentiation increases after treatment with macrophage colony-stimulating factor

impaired macrophage chemotaxis
- to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- mice are protected from bleomycin-induced lung fibrosis with fewer recruited alveolar macrophages in the bronchoalveolar lavage compared with similarly treated wild-type mice

hematopoietic system phenotype

abnormal microglial cell morphology
- decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

decreased macrophage cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice
- numbers are significantly decreased in atral follicles
- numbers were enhanced by treatment with macrophage colony-stimulating factor

impaired macrophage chemotaxis
- to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

nervous system phenotype

abnormal microglial cell morphology
- decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

abnormal neurite morphology
- neurons explanted from embryonic day 17 cortex and cultured for 1 to 2 days have fewer processes and at 4 and 8 days of culture have decreased complexity of neurites compared with controls

hearing/vestibular/ear phenotype

abnormal auditory brainstem response waveform shape
- latencies are prolonged and amplitudes reduced with an absolute delay in the wave I latency, prolongation of the wave I-V interval, and loss of amlitude and integrity of the later components; subcutaneous administration of CSF1 daily for 10 weeks beginning at 2 days of age ameliorates this phenotype toward normal valuesg at 2 days of age ameliorates this phenotype toward normal values

vision/eye phenotype

abnormal visual evoked potential
- administration of the GABA A antagonist bicuculline results not only in changes in neural firing in the supragranular laminae, as is the case in wild-type controls, but also results in diffusely elevated unit firing in several laminae in homozygotes indicating abnormal intracortical circuitryating abnormal intracortical circuitry
- intracortical visual evoked potential readings show total intracortical current to be significantly reduced, both in the initial excitation and subsequent inhibition, with deficits found in both transmembrane current flow and multiple unit activity, although the onset latencies of current flow are normal; subcutaneous administration of CSF1 daily for 10 weeks beginning at 2 days of age ameliorates this phenotype toward normal valuesugh the onset latencies of current flow are normal; subcutaneous administration of CSF1 daily for 10 weeks beginning at 2 days of age ameliorates this phenotype toward normal values
- supragranular laminae and thalamorecipient layers both show abnormal processing
- surface visual evoked potentials are dramatically reduced or absent

endocrine/exocrine gland phenotype

abnormal ovarian follicle number
- there are fewer atral and mature follicles in the proestrus ovary compared with controls

abnormal ovarian folliculogenesis

decreased mature ovarian follicle number

decreased secondary ovarian follicle number
- fewer follicles develop compared with normal

impaired granulosa cell differentiation
- the numbers of cells in the atral follicles are significantly reduced but differentiation increases after treatment with macrophage colony-stimulating factor

reproductive system phenotype

abnormal ovarian follicle number
- there are fewer atral and mature follicles in the proestrus ovary compared with controls

abnormal ovarian folliculogenesis

abnormal ovulation
- the number of eggs ovulated at each cycle varies significantly
- total number of oocytes ovulated is less than expected

decreased mature ovarian follicle number

decreased secondary ovarian follicle number
- fewer follicles develop compared with normal

impaired granulosa cell differentiation
- the numbers of cells in the atral follicles are significantly reduced but differentiation increases after treatment with macrophage colony-stimulating factor

behavior/neurological phenotype

behavior/neurological phenotype
- mutants do not exhibit any neurological signs

Genotype: Csf1^op/Csf1^op
B6C3Fe a/a-Csf1^op/J

mortality/aging

postnatal lethality, incomplete penetrance
- reduced numbers of homozygotes survive to weaning

endocrine/exocrine gland phenotype

abnormal branching of the mammary ductal tree
- ductal structures are poorly developed with incomplete arborization

abnormal lactation
- only 10% of females can lactate, however, lactation in this subset is inefficient

abnormal mammary gland alveolus morphology
- alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

abnormal mammary gland development
- alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed
- postpartum females exhibit incompletely differentiated mammary gland tissue with a nonsecretory phenotype

abnormal mammary gland growth during pregnancy
- lobulo-alveolar development is premature and occupies 56% of mammary gland by day 18 of pregnancy

increased testis weight
- as a percentage of body weight, testicular tissue is increased over controls

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

thymus medulla atrophy
- atrophic with numerous macrophages

homeostasis/metabolism phenotype

amyloid beta deposits
- 100 to 200 fibrillar plaques observed in cerebral cortex
- 20 to 60 plaques observed in amygdala and hypothalamus
- small number of plaques observed in hippocampus

decreased circulating testosterone level

hearing/vestibular/ear phenotype

abnormal auditory brainstem response
- delayed and diminished response to brainstem auditory evoked potential (BAEP)

abnormal vestibular system physiology
- poorly formed or absent response to surface visual evoked potential (VEP)

cardiovascular system phenotype

abnormal Kupffer cell morphology
- 30% fewer Kupffer cells than normal littermates
- Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections
- irregular distribution of Kupffer cells in liver lobules

abnormal perivascular macrophage morphology
- reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

craniofacial phenotype

abnormal parietal bone morphology
- parietal bone grows only through the trabecular bone formation with no subperiosteal bone lamellae forming as in normal mice

domed cranium
- flat bone grows without resorption while keeping the normal primary curvature resulting in a more globular skull

muscle phenotype

abnormal masseter muscle morphology
- severely atrophied white and intermediate muscle fibers are observed in the superficial region of the masseter muscle
- the decrease in diameter of muscle fibers was larger than found in mice fed a granulated diet
- the decrease in sensory input due to underdevelopment of periodontal ligaments in the absence of teeth likely results in atrophy of the masseter muscle
- the progression and extent of atrophy differed among regions of the muscle

vision/eye phenotype

abnormal visual evoked potential
- altered neural firing as demonstrated by multiple unit activity (MUA) measurement
- total intracortical transmembrane current significantly reduced as measured by intracortical VEP

integument phenotype

abnormal branching of the mammary ductal tree
- ductal structures are poorly developed with incomplete arborization

abnormal lactation
- only 10% of females can lactate, however, lactation in this subset is inefficient

abnormal mammary gland alveolus morphology
- alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

abnormal mammary gland development
- alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed
- postpartum females exhibit incompletely differentiated mammary gland tissue with a nonsecretory phenotype

abnormal mammary gland growth during pregnancy
- lobulo-alveolar development is premature and occupies 56% of mammary gland by day 18 of pregnancy

cellular phenotype

abnormal osteoclast differentiation
- daily injection of exogenous M-CSF recruits functional osteoclasts
- linked to impaired remodeling of bone and no marrow cavity formation in long bones
- minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts

necrospermia
- percentage of dead sperm is two times higher than controls

oligozoospermia
- epididymal sperm count 60% lower than control

growth/size/body region phenotype

decreased body weight
- low body weight

postnatal growth retardation
- slower growth rate

immune system phenotype

abnormal Kupffer cell morphology
- 30% fewer Kupffer cells than normal littermates
- Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections
- irregular distribution of Kupffer cells in liver lobules

abnormal Langerhans cell morphology
- bone chimera experiments suggest hematopoietic precursors to Langerhans cells have reduced capability to differentiate into Langerhan cells when skin is inflammed

abnormal Langerhans cell physiology
- Langerhan cell numbers are slow to recover after UV irradiation
- two weeks after UV irradiation, numbers are 25% compared to unirradiated mutant mice while at the same timepoint irradiated wild-type LC numbers are close to 100% of control

abnormal microglial cell morphology
- microglial cells in frontal cortex have smaller cell bodies and shorter cytoplasmic processes
- reduced numbers of microglial cells in frontal cortex, parietal cortex and corpus callosum

abnormal osteoclast differentiation
- daily injection of exogenous M-CSF recruits functional osteoclasts
- linked to impaired remodeling of bone and no marrow cavity formation in long bones
- minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts

abnormal osteoclast morphology
- reduced size and number of multinuclear osteoclasts

abnormal perivascular macrophage morphology
- reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

abnormal spleen red pulp morphology
- extensive extramedullary hematopoiesis

abnormal splenic cell ratio
- increased concentration of CFU-S cells, however , size and differentiation pattern of spleen colonies is normal
- reduced number of macrophages
- spleen mostly composed of fibroblastoid cells

abnormal splenocyte physiology
- mutants have prolonged hemopoiesis

absent Langerhans cell
- absence of Langerhans cells in newborns but numbers recover in adults

decreased leukocyte cell number

decreased macrophage cell number
- decreased numbers in spleen and marrow
- decreased numbers of macrophages in liver, spleen, bone marrow, kidney, subcutaneous tissue, uterus and ovary
- macrophage organelles and microvillous projections are poorly developed
- macrophages exhibit intracytoplasmic organelles in splenic, thymic and bone marrow

decreased monocyte cell number
- almost complete absence of monocytes in peripheral blood

decreased osteoclast cell number
- TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

thymus medulla atrophy
- atrophic with numerous macrophages

skeleton phenotype

abnormal bone marrow cavity morphology
- apparent at postnatal Day 2 and by Day 7 femoral marrow cellularity and progenitor cell content was significantly reduced
- none in long bones where no bone remodeling occurs
- reduced numbers of hematopoietic cells

abnormal bone marrow morphology
- femoral bone marrow cellularity is reduced early but recovers to control levels by 8 months of age

abnormal bone remodeling
- in long bones, therefore no marrow cavity formation

abnormal femur morphology
- distal end is wide, diaphysis does not have a well defined cortex

abnormal long bone hypertrophic chondrocyte zone

abnormal osteoclast differentiation
- daily injection of exogenous M-CSF recruits functional osteoclasts
- linked to impaired remodeling of bone and no marrow cavity formation in long bones
- minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts

abnormal osteoclast morphology
- reduced size and number of multinuclear osteoclasts

abnormal parietal bone morphology
- parietal bone grows only through the trabecular bone formation with no subperiosteal bone lamellae forming as in normal mice

abnormal tibia morphology
- proximal end is wide, diaphysis does not have a well defined cortex

decreased osteoclast cell number
- TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

domed cranium
- flat bone grows without resorption while keeping the normal primary curvature resulting in a more globular skull

increased bone trabecula number
- excessive amount of bone trabeculae
- higher amounts of bony trabeculae

reproductive system phenotype

abnormal mammary gland growth during pregnancy
- lobulo-alveolar development is premature and occupies 56% of mammary gland by day 18 of pregnancy

abnormal uterus development
- poor development of glandular epithelia

endometrium hypoplasia
- endometrium is hypoplastic

increased testis weight
- as a percentage of body weight, testicular tissue is increased over controls

myometrium hypoplasia
- myometrium is hypoplastic

necrospermia
- percentage of dead sperm is two times higher than controls

oligozoospermia
- epididymal sperm count 60% lower than control

reduced male fertility
- males mate on the first night, but not on subsequent nights in timed mating experiments
- males take 5 times longer to mate than controls

nervous system phenotype

abnormal microglial cell morphology
- microglial cells in frontal cortex have smaller cell bodies and shorter cytoplasmic processes
- reduced numbers of microglial cells in frontal cortex, parietal cortex and corpus callosum

amyloid beta deposits
- 100 to 200 fibrillar plaques observed in cerebral cortex
- 20 to 60 plaques observed in amygdala and hypothalamus
- small number of plaques observed in hippocampus

decreased hippocampus pyramidal cell number
- hippocampal neuron loss in CA1 and CA3 regions

hematopoietic system phenotype

abnormal Kupffer cell morphology
- 30% fewer Kupffer cells than normal littermates
- Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections
- irregular distribution of Kupffer cells in liver lobules

abnormal Langerhans cell morphology
- bone chimera experiments suggest hematopoietic precursors to Langerhans cells have reduced capability to differentiate into Langerhan cells when skin is inflammed

abnormal bone marrow cell morphology/development

abnormal hematopoietic stem cell morphology

abnormal microglial cell morphology
- microglial cells in frontal cortex have smaller cell bodies and shorter cytoplasmic processes
- reduced numbers of microglial cells in frontal cortex, parietal cortex and corpus callosum

abnormal osteoclast differentiation
- daily injection of exogenous M-CSF recruits functional osteoclasts
- linked to impaired remodeling of bone and no marrow cavity formation in long bones
- minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts

abnormal osteoclast morphology
- reduced size and number of multinuclear osteoclasts

abnormal perivascular macrophage morphology
- reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

abnormal spleen red pulp morphology
- extensive extramedullary hematopoiesis

abnormal splenic cell ratio
- increased concentration of CFU-S cells, however , size and differentiation pattern of spleen colonies is normal
- reduced number of macrophages
- spleen mostly composed of fibroblastoid cells

abnormal splenocyte physiology
- mutants have prolonged hemopoiesis

absent Langerhans cell
- absence of Langerhans cells in newborns but numbers recover in adults

decreased bone marrow cell number
- marrow mostly composed of fibroblastoid cells
- number of cells 10 fold less than controls
- reduced numbers of CFU-S cells

decreased leukocyte cell number

decreased macrophage cell number
- decreased numbers in spleen and marrow
- decreased numbers of macrophages in liver, spleen, bone marrow, kidney, subcutaneous tissue, uterus and ovary
- macrophage organelles and microvillous projections are poorly developed
- macrophages exhibit intracytoplasmic organelles in splenic, thymic and bone marrow

decreased monocyte cell number
- almost complete absence of monocytes in peripheral blood

decreased osteoclast cell number
- TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

extramedullary hematopoiesis
- observed in splenic red pulp

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

thymus medulla atrophy
- atrophic with numerous macrophages

liver/biliary system phenotype

abnormal Kupffer cell morphology
- 30% fewer Kupffer cells than normal littermates
- Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections
- irregular distribution of Kupffer cells in liver lobules

limbs/digits/tail phenotype

abnormal femur morphology
- distal end is wide, diaphysis does not have a well defined cortex

abnormal tibia morphology
- proximal end is wide, diaphysis does not have a well defined cortex

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

Genotype: Csf1^op/Csf1^op
C57BL/6J-Csf1^op

mortality/aging

premature death
- 40% of mice that survive weaning die by 12 months
- hydrocephalus is observed in mice that die at an early age

homeostasis/metabolism phenotype

decreased circulating phosphate level
- serum phosphate levels average 30% below control

skeleton phenotype

abnormal bone marrow cavity morphology
- abnormally high numbers of megakaryocytes
- delayed development of bone marrow cavity

abnormal bone structure
- large lipoid masses in vascular and extravascular areas of bone

abnormal osteoblast physiology
- decreased bone matrix formation after day 81
- increased bone matrix formation to postnatal day 40

abnormal osteoclast morphology
- abnormal distribution of acid phosphatase activity
- osteoclasts small and few in number

abnormal skeleton morphology
- overall skeleton is smaller than in wild-type

abnormal trabecular bone morphology
- long bones filled with primary spongiosa

absent incisors
- absence of incisors is observed by 10 days

absent teeth
- homozygous mice are toothless

decreased osteoclast cell number

domed cranium
- observed by 10 days

osteopetrosis

osteoporosis
- mice exhibit osteoporosis

immune system phenotype

abnormal osteoclast morphology
- abnormal distribution of acid phosphatase activity
- osteoclasts small and few in number

abnormal spleen red pulp morphology
- sinusoids less developed

decreased macrophage cell number
- cells expressing F4/80+ (a marker for macrophages) are almost entirely absent

decreased osteoclast cell number

hematopoietic system phenotype

abnormal osteoclast morphology
- abnormal distribution of acid phosphatase activity
- osteoclasts small and few in number

abnormal spleen red pulp morphology
- sinusoids less developed

decreased macrophage cell number
- cells expressing F4/80+ (a marker for macrophages) are almost entirely absent

decreased osteoclast cell number

reproductive system phenotype

reduced fertility

craniofacial phenotype

abnormal snout morphology
- snouts are rounded

absent incisors
- absence of incisors is observed by 10 days

absent teeth
- homozygous mice are toothless

domed cranium
- observed by 10 days

limbs/digits/tail phenotype

abnormal autopod morphology
- all hind foot digits curve progressively laterally or medially
- change in shape of hind feet during growth, first digit of hindfoot often becomes parallel to the second digit

short limbs

short tail
- frequent development of s-type curves

growth/size/body region phenotype

abnormal snout morphology
- snouts are rounded

absent incisors
- absence of incisors is observed by 10 days

absent teeth
- homozygous mice are toothless

slow postnatal weight gain
- from day 10 weight gain does not match control

endocrine/exocrine gland phenotype

abnormal thyroid parafollicular C-cell morphology
- parafollicular cell density in thyroid is significantly increased during first three months

References

Additional References

Bruhns P; Samuelsson A; Pollard JW; Ravetch JV. 2003. Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease. Immunity 18(4):573-81. PubMed: 12705859 MGI: J:83013
Ida-Yonemochi H; Noda T; Shimokawa H; Saku T. 2002. Disturbed tooth eruption in osteopetrotic (op/op) mice: histopathogenesis of tooth malformation and odontomas. J Oral Pathol Med 31(6):361-73. PubMed: 12201247 MGI: J:78487
Kaku M; Tsutsui K; Motokawa M; Kawata T; Fujita T; Kohno S; Tohma Y; Ohtani J; Tenjoh K; Tanne K. 2003. Amyloid beta protein deposition and neuron loss in osteopetrotic (op/op) mice. Brain Res Brain Res Protoc 12(2):104-8. PubMed: 14613812 MGI: J:87261
Lenda DM; Kikawada E; Stanley ER; Kelley VR. 2003. Reduced macrophage recruitment, proliferation, and activation in colony-stimulating factor-1-deficient mice results in decreased tubular apoptosis during renal inflammation. J Immunol 170(6):3254-62. PubMed: 12626584 MGI: J:82301
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Also Known As: osteopetrosis

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Csf1op

Allele Symbol: Csf1op

a

Allele Symbol: a

Disease Terms

Research Areas By Genotype

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

Genotype: Csf1op related

Mammalian Phenotype Terms by Genotype

Genotype: Csf1op/Csf1opinvolves: C3HeB/FeJ * C57BL/6J

homeostasis/metabolism phenotype

reproductive system phenotype

integument phenotype

cellular phenotype

behavior/neurological phenotype

cardiovascular system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

Genotype: Csf1op/Csf1opB6;C3Fe a/a-Csf1op/J

immune system phenotype

growth/size/body region phenotype

cellular phenotype

homeostasis/metabolism phenotype

hematopoietic system phenotype

nervous system phenotype

hearing/vestibular/ear phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

reproductive system phenotype

behavior/neurological phenotype

Genotype: Csf1op/Csf1opB6C3Fe a/a-Csf1op/J

mortality/aging

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

hearing/vestibular/ear phenotype

cardiovascular system phenotype

craniofacial phenotype

muscle phenotype

vision/eye phenotype

integument phenotype

cellular phenotype

growth/size/body region phenotype

immune system phenotype

skeleton phenotype

reproductive system phenotype

nervous system phenotype

hematopoietic system phenotype

liver/biliary system phenotype

limbs/digits/tail phenotype

Genotype: Csf1op/Csf1opC57BL/6J-Csf1op

mortality/aging

homeostasis/metabolism phenotype

skeleton phenotype

immune system phenotype

hematopoietic system phenotype

reproductive system phenotype

craniofacial phenotype

limbs/digits/tail phenotype

growth/size/body region phenotype

endocrine/exocrine gland phenotype

References

Additional References

Additional - a related

Additional - Csf1op related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Csf1^op

Allele Symbol: Csf1^op

Genotype: Csf1^op related

Genotype: Csf1^op/Csf1^op
involves: C3HeB/FeJ * C57BL/6J

Genotype: Csf1^op/Csf1^op
B6;C3Fe a/a-Csf1^op/J

Genotype: Csf1^op/Csf1^op
B6C3Fe a/a-Csf1^op/J

Genotype: Csf1^op/Csf1^op
C57BL/6J-Csf1^op

Additional - Csf1^op related