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
	N81 (2020-09-25 00:00:00)

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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

Research Applications

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

View All Research Applications

Base Price

Starting at:

$278.00 Domestic price for female

483.90 Domestic price for breeder pair

View Price List

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.
Homozygous pups are identifiable by their phenotype at 10 days of age by absence of incisors and by a domed skull. Unfortunately, ~50% of homozygotes die around weaning age. If they are to survive the weaning process, they must be provided with crushed food in the bottom of the cage. A soft rodent diet could also be used. Those that survive weaning may live up to 6 months.

Development

The osteopetrotic mutation (Csf1^op) 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. Since 2010, The Jackson Laboratory live colony has been maintained by breeding mice heterozygous for Csf1^op to B6C3FeF1/J a/a mice (Stock No. 001022).

Control Suggestions

000231 B6;C3Fe a/a-Csf1^op/J, (Wild-type from the colony
)

Additional Information

Considerations for Choosing Controls

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
General Note	Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039
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 (beta4 retroviral sequence). 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.

Csf1^op

Allele Symbol: Csf1^op

Allele Name	osteopetrosis
Allele Type	Spontaneous
Allele Synonym(s)	Csf1^- op; Csf-1^op; Csfm^op; csfmop; M-; op
Gene Symbol and Name	Csf1, colony stimulating factor 1 (macrophage)
Gene Synonym(s)
Strain of Origin	B6;DW-Pou1f1^dw
Chromosome	3
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.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

osteopetrosis

Research Areas By Phenotype

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

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

Genotype: Csf1^op related

Developmental Biology Research
- Skeletal Defects
  - osteopetrosis
Mouse/Human Gene Homologs
- Infantile neuronal ceroid lipofuscinosis
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Macrophage Deficiency
Cancer Research
- Growth Factors/Receptors/Cytokines
Endocrine Deficiency Research
- Bone/Bone Marrow Defects
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Immunodeficiency Associated with Other Defects
- Immunodeficiency

Mammalian Phenotype Terms by Genotype

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

hematopoietic system phenotype

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

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

abnormal spleen red pulp morphology
- sinusoids less developed

decreased osteoclast cell number

homeostasis/metabolism phenotype

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

immune system phenotype

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

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

abnormal spleen red pulp morphology
- sinusoids less developed

decreased osteoclast cell number

cellular phenotype

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

limbs/digits/tail phenotype

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

short tail
- frequent development of s-type curves

short limbs

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

reproductive system phenotype

reduced fertility

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

osteopetrosis

abnormal trabecular bone morphology
- long bones filled with primary spongiosa

osteoporosis
- mice exhibit osteoporosis

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

absent incisors
- absence of incisors is observed by 10 days

decreased osteoclast cell number

absent teeth
- homozygous mice are toothless

domed cranium
- observed by 10 days

craniofacial phenotype

round snout
- snouts are rounded

absent incisors
- absence of incisors is observed by 10 days

domed cranium
- observed by 10 days

absent teeth
- homozygous mice are toothless

endocrine/exocrine gland phenotype

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

growth/size/body region phenotype

absent teeth
- homozygous mice are toothless

absent incisors
- absence of incisors is observed by 10 days

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

round snout
- snouts are rounded

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

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

behavior/neurological phenotype

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

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

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

endocrine/exocrine gland phenotype

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

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

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

decreased corpora lutea number

abnormal mammary gland lobule morphology

abnormal mammary gland development

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

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

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

growth/size/body region phenotype

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

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

hematopoietic system phenotype

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

abnormal osteoclast cell number

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

homeostasis/metabolism phenotype

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

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

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

immune system phenotype

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

abnormal osteoclast cell number

integument phenotype

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

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

abnormal mammary gland lobule morphology

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

abnormal mammary gland development

reproductive system phenotype

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

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

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

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

abnormal ovulation
- significantly lower ovulation rate and frequency

decreased corpora lutea number

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

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

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

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

reduced female fertility

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

skeleton phenotype

abnormal bone remodeling
- 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
- although bone remodeling is reduced, overall decline in rate of bone formation removes excess bone resulting in nearly normal bone

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

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

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

abnormal osteoclast cell number

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

cellular phenotype

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

craniofacial phenotype

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

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

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

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

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 values
- g at 2 days of age ameliorates this phenotype toward normal values

hematopoietic system phenotype

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

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

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

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

mammalian phenotype

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

nervous system phenotype

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

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

reproductive system phenotype

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

abnormal ovarian folliculogenesis

decreased mature ovarian follicle number

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

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

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

vision/eye phenotype

abnormal visual evoked potential
- supragranular laminae and thalamorecipient layers both show abnormal processing
- 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 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 values
- surface visual evoked potentials are dramatically reduced or absent
- ating abnormal intracortical circuitry
- ugh 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

endocrine/exocrine gland phenotype

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

abnormal ovarian folliculogenesis

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

decreased mature ovarian follicle number

growth/size/body region phenotype

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

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

integument phenotype

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

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

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

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

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

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

mortality/aging

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

muscle phenotype

abnormal masseter muscle morphology
- severely atrophied white and intermediate muscle fibers are observed in the superficial region of the masseter muscle
- the progression and extent of atrophy differed among regions of the 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

nervous system phenotype

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

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

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

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

endometrium hypoplasia
- endometrium is hypoplastic

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

abnormal uterus development
- poor development of glandular epithelia

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

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

myometrium hypoplasia
- myometrium is hypoplastic

oligozoospermia
- epididymal sperm count 60% lower than control

skeleton phenotype

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

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

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

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

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

abnormal osteoclast morphology
- reduced size and number of multinuclear osteoclasts

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

abnormal long bone hypertrophic chondrocyte zone

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

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

craniofacial phenotype

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

abnormal masseter muscle morphology
- 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 decrease in diameter of muscle fibers was larger than found in mice fed a granulated diet
- severely atrophied white and intermediate muscle fibers are observed in the superficial region of the masseter muscle
- the progression and extent of atrophy differed among regions of the muscle

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

vision/eye phenotype

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

endocrine/exocrine gland phenotype

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

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

thymus medulla atrophy
- atrophic with numerous macrophages

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

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

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

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

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

cardiovascular system phenotype

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

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

growth/size/body region phenotype

abnormal masseter muscle morphology
- 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
- 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

postnatal growth retardation
- slower growth rate

decreased body weight
- low body weight

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)

hematopoietic system phenotype

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 spleen red pulp morphology
- extensive extramedullary hematopoiesis

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

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

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

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

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

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

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

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

abnormal splenocyte physiology
- mutants have prolonged hemopoiesis

abnormal bone marrow cell morphology/development

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 medulla atrophy
- atrophic with numerous macrophages

abnormal hematopoietic stem cell morphology

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

decreased leukocyte cell number

cellular phenotype

abnormal osteoclast differentiation
- linked to impaired remodeling of bone and no marrow cavity formation in long bones
- daily injection of exogenous M-CSF recruits functional osteoclasts
- 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

homeostasis/metabolism phenotype

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

decreased circulating testosterone level

immune system phenotype

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

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

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

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

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 splenocyte physiology
- mutants have prolonged hemopoiesis

thymus cortex hypoplasia
- consists mostly of thymic epithelial cells

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

decreased leukocyte cell number

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 medulla atrophy
- atrophic with numerous macrophages

abnormal osteoclast morphology
- reduced size and number of multinuclear osteoclasts

abnormal spleen red pulp morphology
- extensive extramedullary hematopoiesis

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

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

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):573-81PubMed: 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):361-73PubMed: 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):104-8PubMed: 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):3254-62PubMed: 12626584 MGI: J:82301
Lenda DM; Stanley ER; Kelley VR. 2004. Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Fas(lpr) mice. J Immunol 173(7):4744-54PubMed: 15383612 MGI: J:93714
Naito M; Hayashi S; Yoshida H; Nishikawa S; Shultz LD; Takahashi K. 1991. Abnormal differentiation of tissue macrophage populations in 'osteopetrosis' (op) mice defective in the production of macrophage colony-stimulating factor. Am J Pathol 139(3):657-67PubMed: 1887865 MGI: J:26978
Sasaki A; Yokoo H; Naito M; Kaizu C; Shultz LD; Nakazato Y. 2000. Effects of macrophage-colony-stimulating factor deficiency on the maturation of microglia and brain macrophages and on their expression of scavenger receptor. Neuropathology 20(2):134-42PubMed: 10935450 MGI: J:82594
Tagaya H; Kunisada T; Yamazaki H; Yamane T; Tokuhisa T; Wagner EF; Sudo T; Shultz LD; Hayashi SI. 2000. Intramedullary and extramedullary B lymphopoiesis in osteopetrotic mice. Blood 95(11):3363-70PubMed: 10828017 MGI: J:82593
Yoshida H; Hayashi S; Kunisada T; Ogawa M; Nishikawa S; Okamura H; Sudo T; Shultz LD; Nishikawa S. 1990. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 345(6274):442-4PubMed: 2188141 MGI: J:10519

Additional - a related

Additional - Csf1^op related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Csf1
- Probe:Csf1 Probe
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

Since 2010, The Jackson Laboratory live colony has been maintained by breeding mice heterozygous for Csf1^op to B6C3FeF1/J a/a mice (Stock No. 001022).
- Additional Breeding and Husbandry Support
Mating System
- Heterozygous x B6C3FeF1/J a/a Stock No. 001022
  B6C3FeF1/J a/a Stock No. 001022 x Heterozygou
Appearance
- black, osteopetrosis
  Related Genotype: a/a Csf1^op/Csf1^op
  
  black, unaffected
  Related Genotype: a/a Csf1^op/+ or a/a ?/+
Citation
When using the osteopetrosis mouse strain in a publication, please cite the originating article(s) and include JAX stock #000231 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

FGB29 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Homozygous for a, Heterozygous or Wild-type for Csf1<op>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

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Credit for PRODUCTS or SERVICES

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Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:osteopetrosis

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

a

Allele Symbol: a

Csf1op

Allele Symbol: Csf1op

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: Csf1op related

Mammalian Phenotype Terms by Genotype

Genotype: Csf1op/Csf1opC57BL/6J-Csf1

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

cellular phenotype

limbs/digits/tail phenotype

mortality/aging

reproductive system phenotype

skeleton phenotype

craniofacial phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

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

behavior/neurological phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

reproductive system phenotype

cardiovascular system phenotype

skeleton phenotype

cellular phenotype

craniofacial phenotype

Genotype: Csf1op/Csf1opB6;C3Fe a/a-Csf1/J

cellular phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

reproductive system phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

Genotype: Csf1op/Csf1opB6C3Fe a/a-Csf1/J

integument phenotype

limbs/digits/tail phenotype

liver/biliary system phenotype

mortality/aging

muscle phenotype

nervous system phenotype

reproductive system phenotype

skeleton phenotype

craniofacial phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

cardiovascular system phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

cellular phenotype

homeostasis/metabolism phenotype

immune system phenotype

References

Additional References

Additional - a related

Additional - Csf1op related

Genotyping Protocols

Dietary Information

Csf1^op

Allele Symbol: Csf1^op

Genotype: Csf1^op related

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

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

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

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

Additional - Csf1^op related