All Phenotypes Csf1<op> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Csf1^op/Csf1^op	B6;C3Fe a/a-Csf1^op/J	MGI:4418684
hm2	Csf1^op/Csf1^op	B6C3Fe a/a-Csf1^op/J	MGI:3610379
hm3	Csf1^op/Csf1^op	C57BL/6J-Csf1^op	MGI:3609667
hm4	Csf1^op/Csf1^op	involves: C3HeB/FeJ * C57BL/6J	MGI:3610499
cx5	Apoe^tm1Unc/Apoe^tm1Unc Csf1^op/Csf1^op	involves: 129P2/OlaHsd * C3HeB/Fe * C57BL/6	MGI:3836254
cx6	Csf1^op/Csf1^op Csf2^tm1Ard/Csf2^tm1Ard	involves: 129P2/OlaHsd * C57BL/6	MGI:2652709
cx7	Csf1^op/Csf1^op Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro	involves: 129S4/SvJae * BALB/cJ * C57BL/6J	MGI:3699098
cx8	Csf1^op/Csf1^op Mpz^tm1Msch/Mpz⁺	involves: 129S7/SvEvBrd * C57BL/6	MGI:3576604
cx9	Csf1^op/Csf1^op Galc^twi/Galc^twi	involves: C3HeB/Fe * C57BL/6J * CE/J	MGI:5003115

Allelic Composition	Csf1^op/Csf1^op
Genetic Background	B6;C3Fe a/a-Csf1^op/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)

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

immune system

impaired macrophage chemotaxis ( J:147697 )

• to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

decreased macrophage cell number ( J:30863 , J:147697 )

• numbers are significantly decreased in atral follicles (J:30863)

• numbers were enhanced by treatment with macrophage colony-stimulating factor (J:30863)

• in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice (J:147697)

abnormal microglial cell morphology ( J:170081 )

• decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:147697 )

• 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

impaired macrophage chemotaxis ( J:147697 )

• to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

decreased macrophage cell number ( J:30863 , J:147697 )

• numbers are significantly decreased in atral follicles (J:30863)

• numbers were enhanced by treatment with macrophage colony-stimulating factor (J:30863)

• in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice (J:147697)

abnormal microglial cell morphology ( J:170081 )

• decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

nervous system

abnormal microglial cell morphology ( J:170081 )

• decrease in numbers of microglia in the white matter of the brain and spinal cord compared to wild-type mice

abnormal neurite morphology ( J:35818 )

• 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

abnormal auditory brainstem response waveform shape ( J:35818 )

• 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

vision/eye

abnormal visual evoked potential ( J:35818 )

• surface visual evoked potentials are dramatically reduced or absent

• 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

• 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

endocrine/exocrine glands

impaired granulosa cell differentiation ( J:30863 )

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

decreased mature ovarian follicle number ( J:30863 )

• there are fewer mature follicles in the proestrus ovary compared with controls

decreased tertiary ovarian follicle number ( J:30863 )

• fewer antral follicles develop compared with controls

abnormal ovarian folliculogenesis ( J:30863 )

reproductive system

impaired granulosa cell differentiation ( J:30863 )

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

decreased mature ovarian follicle number ( J:30863 )

• there are fewer mature follicles in the proestrus ovary compared with controls

decreased tertiary ovarian follicle number ( J:30863 )

• fewer antral follicles develop compared with controls

abnormal ovarian folliculogenesis ( J:30863 )

abnormal ovulation ( J:30863 )

• total number of oocytes ovulated is less than expected

• the number of eggs ovulated at each cycle varies significantly

behavior/neurological

behavior/neurological phenotype ( J:170081 )

N	• mutants do not exhibit any neurological signs

growth/size/body

abnormal postnatal growth ( J:170081 )

• growth of mutants is slower than wild-type mice

cellular

impaired granulosa cell differentiation ( J:30863 )

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

impaired macrophage chemotaxis ( J:147697 )

• to the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

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

Sagittal sections of Csf1^op/Csf1⁺ and Csf1^op/Csf1^op mammary glands

mortality/aging

postnatal lethality, incomplete penetrance ( J:73663 )

• reduced numbers of homozygotes survive to weaning

growth/size/body

abnormal masseter muscle morphology ( J:20589 )

• 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

decreased body weight ( J:73663 , J:104139 )

• low body weight (J:73663)

postnatal growth retardation ( J:73663 )

• slower growth rate

immune system

abnormal Kupffer cell morphology ( J:26978 )

• 30% fewer Kupffer cells than normal littermates

• irregular distribution of Kupffer cells in liver lobules

• Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections

abnormal perivascular macrophage morphology ( J:49613 )

• reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

thymus cortex hypoplasia ( J:26978 )

• consists mostly of thymic epithelial cells

thymus medulla atrophy ( J:26978 )

• atrophic with numerous macrophages

decreased leukocyte cell number ( J:104139 )

decreased macrophage cell number ( J:26978 , J:104139 )

• decreased numbers of macrophages in liver, spleen, bone marrow, kidney, subcutaneous tissue, uterus and ovary (J:26978)

• macrophages exhibit intracytoplasmic organelles in splenic, thymic and bone marrow (J:26978)

• macrophage organelles and microvillous projections are poorly developed (J:26978)

• decreased numbers in spleen and marrow (J:104139)

decreased osteoclast cell number ( J:73663 )

• TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

decreased monocyte cell number ( J:104139 )

• almost complete absence of monocytes in peripheral blood

abnormal Langerhans cell morphology ( J:112594 )

• bone chimera experiments suggest hematopoietic precursors to Langerhans cells have reduced capability to differentiate into Langerhan cells when skin is inflammed

absent Langerhans cell ( J:112594 )

• absence of Langerhans cells in newborns but numbers recover in adults

abnormal microglial cell morphology ( J:49613 )

• 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

abnormal osteoclast morphology ( J:26978 )

• reduced size and number of multinuclear osteoclasts

abnormal osteoclast differentiation ( J:4732 , J:19549 )

• daily injection of exogenous M-CSF recruits functional osteoclasts (J:4732)

• minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts (J:4732)

• linked to impaired remodeling of bone and no marrow cavity formation in long bones (J:19549)

abnormal spleen red pulp morphology ( J:26978 )

• extensive extramedullary hematopoiesis

abnormal splenic cell ratio ( J:104139 )

• increased concentration of CFU-S cells, however , size and differentiation pattern of spleen colonies is normal

• spleen mostly composed of fibroblastoid cells

• reduced number of macrophages

abnormal splenocyte physiology ( J:19549 )

• mutants have prolonged hemopoiesis

abnormal Langerhans cell physiology ( J:112594 )

• 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

skeleton

abnormal parietal bone morphology ( J:18356 )

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

domed cranium ( J:18356 )

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

abnormal osteoclast morphology ( J:26978 )

• reduced size and number of multinuclear osteoclasts

abnormal osteoclast differentiation ( J:4732 , J:19549 )

• daily injection of exogenous M-CSF recruits functional osteoclasts (J:4732)

• minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts (J:4732)

• linked to impaired remodeling of bone and no marrow cavity formation in long bones (J:19549)

decreased osteoclast cell number ( J:73663 )

• TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

abnormal femur morphology ( J:18356 )

• distal end is wide, diaphysis does not have a well defined cortex

abnormal tibia morphology ( J:26978 )

• proximal end is wide, diaphysis does not have a well defined cortex

abnormal long bone hypertrophic chondrocyte zone ( J:26978 )

abnormal bone marrow cavity morphology ( J:19549 , J:26978 )

• none in long bones where no bone remodeling occurs (J:19549)

• apparent at postnatal Day 2 and by Day 7 femoral marrow cellularity and progenitor cell content was significantly reduced (J:19549)

• reduced numbers of hematopoietic cells (J:26978)

abnormal bone marrow morphology ( J:73663 )

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

increased bone trabecula number ( J:26978 , J:73663 )

• excessive amount of bone trabeculae (J:26978)

• higher amounts of bony trabeculae (J:73663)

abnormal bone remodeling ( J:19549 )

• in long bones, therefore no marrow cavity formation

reproductive system

necrospermia ( J:34371 )

• percentage of dead sperm is two times higher than controls

oligozoospermia ( J:34371 )

• epididymal sperm count 60% lower than control

abnormal mammary gland growth during pregnancy ( J:20519 )

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

increased testis weight ( J:34371 )

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

endometrium hypoplasia ( J:26978 )

• endometrium is hypoplastic

myometrium hypoplasia ( J:26978 )

• myometrium is hypoplastic

abnormal uterine epithelium development ( J:26978 )

• poor development of glandular epithelia

reduced male fertility ( J:34371 )

• males take 5 times longer to mate than controls

• males mate on the first night, but not on subsequent nights in timed mating experiments

nervous system

abnormal microglial cell morphology ( J:49613 )

• 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 ( J:87261 )

• 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 ( J:87261 )

• hippocampal neuron loss in CA1 and CA3 regions

hematopoietic system

abnormal Kupffer cell morphology ( J:26978 )

• 30% fewer Kupffer cells than normal littermates

• irregular distribution of Kupffer cells in liver lobules

• Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections

abnormal perivascular macrophage morphology ( J:49613 )

• reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

thymus cortex hypoplasia ( J:26978 )

• consists mostly of thymic epithelial cells

thymus medulla atrophy ( J:26978 )

• atrophic with numerous macrophages

extramedullary hematopoiesis ( J:26978 )

• observed in splenic red pulp

abnormal bone marrow cell morphology/development ( J:19549 )

decreased bone marrow cell number ( J:104139 )

• number of cells 10 fold less than controls

• marrow mostly composed of fibroblastoid cells

• reduced numbers of CFU-S cells

decreased leukocyte cell number ( J:104139 )

decreased macrophage cell number ( J:26978 , J:104139 )

• decreased numbers of macrophages in liver, spleen, bone marrow, kidney, subcutaneous tissue, uterus and ovary (J:26978)

• macrophages exhibit intracytoplasmic organelles in splenic, thymic and bone marrow (J:26978)

• macrophage organelles and microvillous projections are poorly developed (J:26978)

• decreased numbers in spleen and marrow (J:104139)

decreased osteoclast cell number ( J:73663 )

• TRAP+ cells (osteoclasts) were present in low numbers in the bony trabecula regions compared to controls

decreased monocyte cell number ( J:104139 )

• almost complete absence of monocytes in peripheral blood

abnormal hematopoietic stem cell morphology ( J:19549 )

abnormal Langerhans cell morphology ( J:112594 )

• bone chimera experiments suggest hematopoietic precursors to Langerhans cells have reduced capability to differentiate into Langerhan cells when skin is inflammed

absent Langerhans cell ( J:112594 )

• absence of Langerhans cells in newborns but numbers recover in adults

abnormal microglial cell morphology ( J:49613 )

• 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

abnormal osteoclast morphology ( J:26978 )

• reduced size and number of multinuclear osteoclasts

abnormal osteoclast differentiation ( J:4732 , J:19549 )

• daily injection of exogenous M-CSF recruits functional osteoclasts (J:4732)

• minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts (J:4732)

• linked to impaired remodeling of bone and no marrow cavity formation in long bones (J:19549)

abnormal spleen red pulp morphology ( J:26978 )

• extensive extramedullary hematopoiesis

abnormal splenic cell ratio ( J:104139 )

• increased concentration of CFU-S cells, however , size and differentiation pattern of spleen colonies is normal

• spleen mostly composed of fibroblastoid cells

• reduced number of macrophages

abnormal splenocyte physiology ( J:19549 )

• mutants have prolonged hemopoiesis

liver/biliary system

abnormal Kupffer cell morphology ( J:26978 )

• 30% fewer Kupffer cells than normal littermates

• irregular distribution of Kupffer cells in liver lobules

• Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections

limbs/digits/tail

abnormal femur morphology ( J:18356 )

• distal end is wide, diaphysis does not have a well defined cortex

abnormal tibia morphology ( J:26978 )

• proximal end is wide, diaphysis does not have a well defined cortex

endocrine/exocrine glands

thymus cortex hypoplasia ( J:26978 )

• consists mostly of thymic epithelial cells

thymus medulla atrophy ( J:26978 )

• atrophic with numerous macrophages

abnormal mammary gland development ( J:20519 )

• postpartum females exhibit incompletely differentiated mammary gland tissue with a nonsecretory phenotype

• alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

abnormal branching of the mammary ductal tree ( J:20519 )

• ductal structures are poorly developed with incomplete arborization

abnormal mammary gland growth during pregnancy ( J:20519 )

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

abnormal mammary gland alveolus morphology ( J:20519 )

• alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

increased testis weight ( J:34371 )

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

abnormal lactation ( J:20519 )

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

homeostasis/metabolism

amyloid beta deposits ( J:87261 )

• 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 ( J:34371 )

hearing/vestibular/ear

abnormal auditory brainstem response ( J:19549 )

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

abnormal vestibular system physiology ( J:19549 )

• poorly formed or absent response to surface visual evoked potential (VEP)

cardiovascular system

abnormal Kupffer cell morphology ( J:26978 )

• 30% fewer Kupffer cells than normal littermates

• irregular distribution of Kupffer cells in liver lobules

• Kupffer cells possess phagocytized blood cells, poorly developed organelles and microvilli projections

abnormal perivascular macrophage morphology ( J:49613 )

• reduced numbers of perivascular macrophages (as identified by F4/80 staining) are found in parietal cortex

craniofacial

abnormal parietal bone morphology ( J:18356 )

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

domed cranium ( J:18356 )

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

abnormal masseter muscle morphology ( J:20589 )

• 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

muscle

abnormal masseter muscle morphology ( J:20589 )

• 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

vision/eye

abnormal visual evoked potential ( J:19549 )

• total intracortical transmembrane current significantly reduced as measured by intracortical VEP

• altered neural firing as demonstrated by multiple unit activity (MUA) measurement

integument

abnormal mammary gland development ( J:20519 )

• postpartum females exhibit incompletely differentiated mammary gland tissue with a nonsecretory phenotype

• alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

abnormal branching of the mammary ductal tree ( J:20519 )

• ductal structures are poorly developed with incomplete arborization

abnormal mammary gland growth during pregnancy ( J:20519 )

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

abnormal mammary gland alveolus morphology ( J:20519 )

• alveolar cells are cuboidal, contain large lipid vesicles and the lumen is small or unformed

abnormal lactation ( J:20519 )

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

cellular

necrospermia ( J:34371 )

• percentage of dead sperm is two times higher than controls

oligozoospermia ( J:34371 )

• epididymal sperm count 60% lower than control

abnormal osteoclast differentiation ( J:4732 , J:19549 )

• daily injection of exogenous M-CSF recruits functional osteoclasts (J:4732)

• minimally a single injection of 5 micrograms rhM-CSF is needed for transient recruitment of osteoclasts (J:4732)

• linked to impaired remodeling of bone and no marrow cavity formation in long bones (J:19549)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
osteopetrosis		DOID:13533	OMIM:PS259700 OMIM:PS607634	J:26978

Allelic Composition	Csf1^op/Csf1^op
Genetic Background	C57BL/6J-Csf1^op

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)

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

cellular

abnormal osteoblast physiology ( J:5634 )

• increased bone matrix formation to postnatal day 40

• decreased bone matrix formation after day 81

mortality/aging

premature death ( J:5634 )

• 40% of mice that survive weaning die by 12 months

• hydrocephalus is observed in mice that die at an early age

skeleton

abnormal osteoblast physiology ( J:5634 )

• increased bone matrix formation to postnatal day 40

• decreased bone matrix formation after day 81

abnormal skeleton morphology ( J:110981 )

• overall skeleton is smaller than in wild-type

absent incisors ( J:5634 )

• absence of incisors is observed by 10 days

absent teeth ( J:110981 )

• homozygous mice are toothless

domed cranium ( J:5634 )

• observed by 10 days

abnormal bone structure ( J:5634 )

• large lipoid masses in vascular and extravascular areas of bone

abnormal osteoclast morphology ( J:5634 )

• osteoclasts small and few in number

• abnormal distribution of acid phosphatase activity

decreased osteoclast cell number ( J:5634 )

abnormal bone marrow cavity morphology ( J:5634 )

• delayed development of bone marrow cavity

• abnormally high numbers of megakaryocytes

abnormal trabecular bone morphology ( J:5634 )

• long bones filled with primary spongiosa

osteoporosis ( J:110981 )

• mice exhibit osteoporosis

osteopetrosis ( J:5634 )

immune system

decreased macrophage cell number ( J:110981 )

• cells expressing F4/80+ (a marker for macrophages) are almost entirely absent

abnormal osteoclast morphology ( J:5634 )

• osteoclasts small and few in number

• abnormal distribution of acid phosphatase activity

decreased osteoclast cell number ( J:5634 )

abnormal spleen red pulp morphology ( J:5634 )

• sinusoids less developed

hematopoietic system

decreased macrophage cell number ( J:110981 )

• cells expressing F4/80+ (a marker for macrophages) are almost entirely absent

abnormal osteoclast morphology ( J:5634 )

• osteoclasts small and few in number

• abnormal distribution of acid phosphatase activity

decreased osteoclast cell number ( J:5634 )

abnormal spleen red pulp morphology ( J:5634 )

• sinusoids less developed

reproductive system

reduced fertility ( J:5634 )

craniofacial

absent incisors ( J:5634 )

• absence of incisors is observed by 10 days

absent teeth ( J:110981 )

• homozygous mice are toothless

domed cranium ( J:5634 )

• observed by 10 days

round snout ( J:110981 )

• snouts are rounded

limbs/digits/tail

abnormal autopod morphology ( J:5634 )

• 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 ( J:5634 )

short tail ( J:5634 )

• frequent development of s-type curves

growth/size/body

absent incisors ( J:5634 )

• absence of incisors is observed by 10 days

absent teeth ( J:110981 )

• homozygous mice are toothless

round snout ( J:110981 )

• snouts are rounded

slow postnatal weight gain ( J:5634 )

• from day 10 weight gain does not match control

endocrine/exocrine glands

abnormal thyroid parafollicular C-cell morphology ( J:5634 )

• parafollicular cell density in thyroid is significantly increased during first three months

homeostasis/metabolism

decreased circulating phosphate level ( J:5634 )

• serum phosphate levels average 30% below control

Allelic Composition	Csf1^op/Csf1^op
Genetic Background	involves: C3HeB/FeJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)

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

homeostasis/metabolism

decreased circulating testosterone level ( J:34371 )

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

abnormal circulating calcium level ( J:5634 )

• unable to raise serum calcium concentration in response to parathyroid extract (PTE)

decreased circulating phosphate level ( J:5634 )

• phosphate serum levels are low but calcium levels are normal

behavior/neurological

abnormal eating behavior ( J:40136 )

• pups drink less of the mother's milk possibly due to being unable to compete with normal littermates

abnormal mating frequency ( J:38039 )

• 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 ( J:34371 )

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

cardiovascular system

decreased susceptibility to atherosclerosis ( J:40136 )

• mice on a high fat diet for 15 weeks develop smaller atherosclerosis lesions than do the C57BL/6J controls

• lesions are also less frequent and when present, less advanced with no lesions containing fibrous caps observed

growth/size/body

absent teeth ( J:5634 )

• noticeably absent at 10 days of age

• at weaning mice need to be provided with soft food in order to thrive

decreased body weight ( J:40136 )

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

hematopoietic system

abnormal osteoclast differentiation ( J:38039 )

• exogenous M-CSF enables normal osteoclast differentiation

abnormal osteoclast cell number ( J:33189 )

decreased osteoclast cell number ( J:33189 )

• 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

abnormal osteoclast differentiation ( J:38039 )

• exogenous M-CSF enables normal osteoclast differentiation

abnormal osteoclast cell number ( J:33189 )

decreased osteoclast cell number ( J:33189 )

• 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

abnormal osteoclast differentiation ( J:38039 )

• exogenous M-CSF enables normal osteoclast differentiation

absent teeth ( J:5634 )

• noticeably absent at 10 days of age

• at weaning mice need to be provided with soft food in order to thrive

domed cranium ( J:5634 )

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

abnormal osteoclast cell number ( J:33189 )

decreased osteoclast cell number ( J:33189 )

• 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 bone marrow cavity morphology ( J:5634 )

• the excessive accumulations of bone lack marrow cavities

abnormal bone remodeling ( J:5634 )

• 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

craniofacial

absent teeth ( J:5634 )

• noticeably absent at 10 days of age

• at weaning mice need to be provided with soft food in order to thrive

domed cranium ( J:5634 )

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

endocrine/exocrine glands

abnormal thyroid parafollicular C-cell morphology ( J:5634 )

• this cell population is increased in this mutation

abnormal mammary gland development ( J:20519 )

abnormal branching of the mammary ductal tree ( J:20519 )

• precocious development of the lobulo-alveolar system

abnormal mammary gland growth during lactation ( J:20519 )

• incomplete mammary gland ductal growth occurs during pregnancy

abnormal mammary gland lobule morphology ( J:20519 )

abnormal ovary morphology ( J:38039 )

• very few macrophages present in ovaries at all stages of cycle and follicular development

decreased corpora lutea number ( J:38039 )

abnormal lactation ( J:20519 )

• milk proteins are expressed but parturition does not initiate lactation

abnormal testis physiology ( J:34371 )

• testosterone level in the tesis is lower than normal

reproductive system

abnormal ovary morphology ( J:38039 )

• very few macrophages present in ovaries at all stages of cycle and follicular development

decreased corpora lutea number ( J:38039 )

abnormal testis physiology ( J:34371 )

• testosterone level in the tesis is lower than normal

abnormal sperm number ( J:34371 )

• 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 ovulation ( J:38039 )

• significantly lower ovulation rate and frequency

decreased ovulation rate ( J:38039 )

• 20% of ovaries fail to undergo ovulation

• the ovulation rate is low for mice that do ovulate

abnormal proestrus ( J:38039 )

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

prolonged estrous cycle ( J:38039 )

• 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

impaired embryo implantation ( J:38039 )

• a lower than normal number of implantations are seen

reduced female fertility ( J:38039 )

decreased litter size ( J:38039 )

decreased fertilization frequency ( J:38039 )

• only 50% of the mated superovulated mutant females produced fertilized ooctyes compared with 83.3% of the mated superovulated heterozygous females

integument

abnormal mammary gland development ( J:20519 )

abnormal branching of the mammary ductal tree ( J:20519 )

• precocious development of the lobulo-alveolar system

abnormal mammary gland growth during lactation ( J:20519 )

• incomplete mammary gland ductal growth occurs during pregnancy

abnormal mammary gland lobule morphology ( J:20519 )

abnormal lactation ( J:20519 )

• milk proteins are expressed but parturition does not initiate lactation

cellular

abnormal osteoclast differentiation ( J:38039 )

• exogenous M-CSF enables normal osteoclast differentiation

Allelic Composition	Apoe^tm1Unc/Apoe^tm1Unc Csf1^op/Csf1^op
Genetic Background	involves: 129P2/OlaHsd * C3HeB/Fe * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^tm1Unc mutation (33 available); any Apoe mutation (158 available)
Csf1^op mutation (1 available); any Csf1 mutation (48 available)

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

cardiovascular system

decreased susceptibility to atherosclerosis ( J:40136 )

• mice are almost entirely free of fatty lesions in the aortic root compared to the 75% of atherosclerotic lesions in mice homozygote null for just the Apoe gene

homeostasis/metabolism

increased circulating cholesterol level ( J:40136 )

• total cholesterol levels are extremely high with a mean of 1056 mg/dl compared to 112 mg/dl for controls or 379 mg/dl mice for Apoe null mice

Allelic Composition	Csf1^op/Csf1^op Csf2^tm1Ard/Csf2^tm1Ard
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)
Csf2^tm1Ard mutation (3 available); any Csf2 mutation (35 available)

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

mortality/aging

premature death ( J:19089 )

• median survival is 71 days due to pneumonia

craniofacial

absent teeth ( J:19089 )

immune system

increased neutrophil cell number ( J:19089 )

• elevated neutrophil levels in mice 138-170 days of age

decreased leukocyte cell number ( J:19089 )

• lymphopenia, but to a similar level as single Csf1^op mice

lung inflammation ( J:19089 )

• perivascular lymphoid infiltrate in lungs

• lungs of older mutants contain large numbers of alveolar macrophages

interstitial pneumonia ( J:19089 )

• acute broncho- or lobar-pneumonia

• acute multifocal bronchopneumonia contains many neutrophils in the inflammatory exudate

respiratory system

lung inflammation ( J:19089 )

• perivascular lymphoid infiltrate in lungs

• lungs of older mutants contain large numbers of alveolar macrophages

interstitial pneumonia ( J:19089 )

• acute broncho- or lobar-pneumonia

• acute multifocal bronchopneumonia contains many neutrophils in the inflammatory exudate

abnormal pulmonary alveolus morphology ( J:19089 )

• presence of granular, eosinophilic material within lung alveoli that accumulates with age

• aggregates of fibrillary material and numerous type-C lamellar bodies within alveoli

pulmonary alveolar proteinosis ( J:19089 )

• marked accumulation of lipo-proteinaceous alveolar material

skeleton

absent teeth ( J:19089 )

abnormal bone marrow morphology ( J:19089 )

• hypoplasia of femoral bone marrow, although marrow cellularity does increase in older mice

osteopetrosis ( J:19089 )

hematopoietic system

extramedullary hematopoiesis ( J:19089 )

• active extramedullary hematopoiesis in the spleen

polycythemia ( J:19089 )

increased hemoglobin content ( J:19089 )

increased neutrophil cell number ( J:19089 )

• elevated neutrophil levels in mice 138-170 days of age

decreased leukocyte cell number ( J:19089 )

• lymphopenia, but to a similar level as single Csf1^op mice

homeostasis/metabolism

pulmonary alveolar proteinosis ( J:19089 )

• marked accumulation of lipo-proteinaceous alveolar material

growth/size/body

absent teeth ( J:19089 )

Allelic Composition	Csf1^op/Csf1^op Sh3bp2^tm1Bjro/Sh3bp2^tm1Bjro
Genetic Background	involves: 129S4/SvJae * BALB/cJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)
Sh3bp2^tm1Bjro mutation (0 available); any Sh3bp2 mutation (35 available)

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

skeleton

skeleton phenotype ( J:117880 )

N	• the cortical bone resorption seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

immune system

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

abnormal lymph node cell ratio ( J:117880 )

• increase in macrophage numbers in the lymph nodes similar to what is seen in mice homozygous for the Sh3bp2 allele alone

liver inflammation ( J:117880 )

• inflammation is still present but the severity is greatly reduced compared to mice homozygous for the Sh3bp2 allele alone

• however, inflammation of the stomach mucosa seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

liver/biliary system

liver inflammation ( J:117880 )

• inflammation is still present but the severity is greatly reduced compared to mice homozygous for the Sh3bp2 allele alone

• however, inflammation of the stomach mucosa seen in mice homozygous for the Sh3bp2 allele alone is practically eliminated

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:117880 )

• serum levels of TNF are elevated similar to what is seen in mice homozygous for the Sh3bp2 allele alone

Allelic Composition	Csf1^op/Csf1^op Mpz^tm1Msch/Mpz⁺
Genetic Background	involves: 129S7/SvEvBrd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)
Mpz^tm1Msch mutation (0 available); any Mpz mutation (28 available)

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

nervous system

abnormal myelination ( J:67581 )

• although demyelination still occurs it is much reduced in the absence of a wild-type Csf1 allele

• myelin sheaths are thicker than in the absence of a wild-type Csf1 allele

immune system

immune system phenotype ( J:67581 )

N	• macrophage infiltration of motor nerves does not occur

Allelic Composition	Csf1^op/Csf1^op Galc^twi/Galc^twi
Genetic Background	involves: C3HeB/Fe * C57BL/6J * CE/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Csf1^op mutation (1 available); any Csf1 mutation (48 available)
Galc^twi mutation (1 available); any Galc mutation (46 available)

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

mortality/aging

premature death ( J:170081 )

• mutants have a shorter lifespan than single homozygous Galc^twi mice, with a more exacerbated neurological phenotype

behavior/neurological

tremors ( J:170081 )

• mutants develop fine twitching in the neck around P18, 2-3 days earlier than Galc^twi mice, and shortly after develop a coarse tremor that gradually spreads from the neck to the trunk

hindlimb paralysis ( J:170081 )

• moribund mice are paralyzed in the hindlimbs

craniofacial

absent incisors ( J:170081 )

domed cranium ( J:170081 )

growth/size/body

absent incisors ( J:170081 )

decreased body size ( J:170081 )

• smaller than either single mutant

weight loss ( J:170081 )

• mutants start to lose weight between P29 and P33

immune system

impaired macrophage chemotaxis ( J:170081 )

• macrophage infiltration in the CNS white matter observed in Galc^twi mice is almost completely blocked: although degenerated myelin is observed in the white matter parenchyma, PAS stain is rarely seen, indicating that PAS+ macrophages, or globoid cells are not observed in demyelinated lesions and that there is an absence of myelin phagocytosis by macrophages

nervous system

decreased oligodendrocyte progenitor number ( J:170081 )

• white matter exhibits similar reactive astrocytosis as single Galc^twi mice, however double mutants have a smaller oligodendrocyte progenitor cell (OPC) population

abnormal forebrain morphology ( J:170081 )

• levels of psychosine are increased in the forebrain compared to wild-type mice, however levels are lower than in single Galc^twi mice, indicating that levels of psychosine do not correlate with the severity of disease

• mutants have lower levels of free sphingosine compared to wild-type mice, and levels are lower in double mutants than in single Galc^twi mice

abnormal oligodendrocyte morphology ( J:170081 )

• oligodendrocyte progenitor cells become hypertrophic and have short and stout processes instead of well branched fine processes as in wild-type mice

decreased oligodendrocyte number ( J:170081 )

• mutants exhibit fewer oligodendrocytes than wild-type or single Galc^twi mice

abnormal oligodendrocyte physiology ( J:170081 )

• recruitment of oligodendrocyte progenitor cells in response to demyelination is compromised

demyelination ( J:170081 )

• mutants exhibit a more severe demyelinating pathology than single homozygous Galc^twi mice due to inhibition of remyelination and a delay in myelin development, rather than enhanced demyelination

• myelin degeneration is seen in the white matter, with significantly more nonmyelinated axons at P45 in mutants than single Galc^twi mice and a preferential loss of myelin in large diameter axons

• sciatic nerves are severely demyelinated

• however, development (wrapping) of myelin from P15 to P30 is not affected

skeleton

absent incisors ( J:170081 )

domed cranium ( J:170081 )

cellular

decreased oligodendrocyte progenitor number ( J:170081 )

• white matter exhibits similar reactive astrocytosis as single Galc^twi mice, however double mutants have a smaller oligodendrocyte progenitor cell (OPC) population

impaired macrophage chemotaxis ( J:170081 )

hematopoietic system

impaired macrophage chemotaxis ( J:170081 )

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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