Phenotypes Associated with This Genotype

Genotype
MGI:3610379

• Allelic Composition: Csf1^op/Csf1^op
• Genetic Background: B6C3Fe a/a-Csf1^op/J

• ♀: 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 )

• small number of plaques observed in hippocampus

• 100 to 200 fibrillar plaques observed in cerebral cortex

• 20 to 60 plaques observed in amygdala and hypothalamus

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