Phenotypes associated with this allele

• Allele Symbol: Csf1r^tm1Ers
• Allele Name: targeted mutation 1, E Richard Stanley
• Allele ID: MGI:2181194
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Csf1r^tm1Ers/Csf1r^tm1Ers	FVB.129X1-Csf1r^tm1Ers	MGI:3696842
hm2	Csf1r^tm1Ers/Csf1r^tm1Ers	involves: 129X1/SvJ * C3Heb/FeJ * C57BL/6J	MGI:3696841
ht3	Csf1r^tm1Ers/Csf1r^+	B6.129X1-Csf1r^tm1Ers	MGI:5789537

Genotype
MGI:3696842

hm1

• Allelic Composition: Csf1r^tm1Ers/Csf1r^tm1Ers
• Genetic Background: FVB.129X1-Csf1r^tm1Ers

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

mortality/aging

postnatal lethality, complete penetrance ( J:111489 )

• Background Sensitivity: all homozygotes die within the first month of life

limbs/digits/tail

abnormal limb morphology ( J:111489 )

• 40% with obvious limb deformities resulting from spontaneous fractures of long bones

skeleton

abnormal skeleton morphology ( J:111489 )

abnormal osteoclast morphology ( J:111489 )

• no cells with typical osteoclast structure

• some small cells present with multiple or lobulate nuclei but lacking "ruffled" boundries, more like megakaryocytes in appearance

abnormal long bone epiphyseal plate morphology ( J:111489 )

abnormal long bone epiphyseal plate proliferative zone ( J:111489 )

• expanded

increased width of hypertrophic chondrocyte zone ( J:111489 )

• expanded

abnormal compact bone morphology ( J:111489 )

• no clear demarcation of cortical bone from trabecular bone

• disorganized in structure

• collagen fibril disorganized, deposited at various angles, as short, loose fibril clusters

abnormal compact bone lamellar structure ( J:111489 )

• collagen lacks typical lamellar structure

decreased compact bone thickness ( J:111489 )

abnormal osteoblast morphology ( J:111489 )

• randomly clustered rather than the highly organized distribution usually seen

abnormal osteocyte morphology ( J:111489 )

• osteocytes display a more disrupted cytoplasm with numerous vacuolar structures

• groups of several osteocytes are frequently embedded and clustered within a small area of matrix

abnormal osteocyte dendritic process morphology ( J:111489 )

• in tibial sections, all osteocytes lack regular structured processes within canuliculae in the surrounding disorganized matrix

abnormal skeleton physiology ( J:111489 )

abnormal bone ossification ( J:111489 )

decreased bone mineralization ( J:111489 )

• secondary ossification centers of long bones and vertebrae show reduced mineralization

delayed endochondral bone ossification ( J:111489 )

• mineralization of cartilage is delayed

decreased bone strength ( J:111489 )

• bones weak as measured by ultimate load, yield load, and stiffness of femurs

fragile skeleton ( J:111489 )

hematopoietic system

abnormal macrophage differentiation ( J:112594 )

• peritoneal, kidney and dermal macrophages are reduced in number when mutant bone marrow is injected into irradiated wild-type mice

absent Langerhans cell ( J:112594 )

• absence of Langerhans cells at 3 weeks of age

abnormal osteoclast morphology ( J:111489 )

• no cells with typical osteoclast structure

• some small cells present with multiple or lobulate nuclei but lacking "ruffled" boundries, more like megakaryocytes in appearance

immune system

abnormal macrophage differentiation ( J:112594 )

• peritoneal, kidney and dermal macrophages are reduced in number when mutant bone marrow is injected into irradiated wild-type mice

absent Langerhans cell ( J:112594 )

• absence of Langerhans cells at 3 weeks of age

abnormal osteoclast morphology ( J:111489 )

• no cells with typical osteoclast structure

• some small cells present with multiple or lobulate nuclei but lacking "ruffled" boundries, more like megakaryocytes in appearance

abnormal Langerhans cell physiology ( J:112594 )

• mutant bone marrow is unable to resupply Langerhan cell population in UV-irradiated skin when transferred into immunocompromised mice

cellular

abnormal macrophage differentiation ( J:112594 )

• peritoneal, kidney and dermal macrophages are reduced in number when mutant bone marrow is injected into irradiated wild-type mice

Genotype
MGI:3696841

hm2

• Allelic Composition: Csf1r^tm1Ers/Csf1r^tm1Ers
• Genetic Background: involves: 129X1/SvJ * C3Heb/FeJ * C57BL/6J

mortality/aging

postnatal lethality ( J:73663 )

• Background Sensitivity: reduced numbers of homozygotes survive to weaning

growth/size/body

failure of tooth eruption ( J:73663 )

decreased body weight ( J:73663 )

• low body weight

postnatal growth retardation ( J:73663 )

• slower growth rate

increased spleen weight ( J:73663 )

craniofacial

failure of tooth eruption ( J:73663 )

domed cranium ( J:73663 )

limbs/digits/tail

short limbs ( J:73663 )

• truncated

kinked tail ( J:73663 )

• occasionally

skeleton

abnormal skeleton morphology ( J:73663 )

failure of tooth eruption ( J:73663 )

domed cranium ( J:73663 )

decreased length of long bones ( J:73663 )

abnormal bone structure ( J:73663 )

abnormal osteoclast differentiation ( J:73663 )

• fail to develop normally

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 mineral density ( J:73663 )

• increased bone density at metaphyses and in the mandible

• due to failure in development of osteoclasts

abnormal trabecular bone morphology ( J:73663 )

• higher levels of trabecular bone

osteopetrosis ( J:73663 )

failure of bone resorption ( J:73663 )

• impaired bone resorption leads to skeletal deformities

homeostasis/metabolism

abnormal circulating cytokine level ( J:73663 )

• 20 fold increase in circulating levels of colony stimulating factor 1 (CSF1)

hematopoietic system

abnormal osteoclast differentiation ( J:73663 )

• fail to develop normally

abnormal blood cell morphology/development ( J:73663 )

abnormal leukocyte cell number ( J:73663 )

• total cellularity of pleural and peritoneal cavities is reduced

increased granulocyte number ( J:73663 )

decreased Langerhans cell number ( J:73663 )

• decreased numbers of Langerhans cells in epidermis

decreased lymphocyte cell number ( J:73663 )

decreased macrophage cell number ( J:73663 )

• tissue macrophage levels are reduced particularly in the liver

decreased monocyte cell number ( J:73663 )

abnormal spleen morphology ( J:73663 )

• increased numbers of BFU-E and HPP-CFC

increased spleen weight ( J:73663 )

reproductive system

oligozoospermia ( J:73663 )

♂ • reduced sperm count

abnormal mammary gland growth during pregnancy ( J:73663 )

♀ • failed branching morphogenesis

decreased testes secretion ( J:73663 )

♂ • low testosterone levels

prolonged diestrus ( J:73663 )

♀

prolonged estrous cycle ( J:73663 )

♀ • longer estrus cycle due to prolonged diestrus

reduced male fertility ( J:73663 )

♂ • males mate less frequently and fewer pregnancies result

behavior/neurological

abnormal sexual interaction ( J:73663 )

♂ • males mate less frequently

hearing/vestibular/ear

deafness ( J:73663 )

• mice are deaf

immune system

abnormal osteoclast differentiation ( J:73663 )

• fail to develop normally

abnormal leukocyte cell number ( J:73663 )

• total cellularity of pleural and peritoneal cavities is reduced

increased granulocyte number ( J:73663 )

decreased Langerhans cell number ( J:73663 )

• decreased numbers of Langerhans cells in epidermis

decreased lymphocyte cell number ( J:73663 )

decreased macrophage cell number ( J:73663 )

• tissue macrophage levels are reduced particularly in the liver

decreased monocyte cell number ( J:73663 )

abnormal spleen morphology ( J:73663 )

• increased numbers of BFU-E and HPP-CFC

increased spleen weight ( J:73663 )

abnormal circulating cytokine level ( J:73663 )

• 20 fold increase in circulating levels of colony stimulating factor 1 (CSF1)

endocrine/exocrine glands

abnormal mammary gland growth during pregnancy ( J:73663 )

♀ • failed branching morphogenesis

decreased testes secretion ( J:73663 )

♂ • low testosterone levels

integument

abnormal mammary gland growth during pregnancy ( J:73663 )

♀ • failed branching morphogenesis

cellular

oligozoospermia ( J:73663 )

♂ • reduced sperm count

abnormal osteoclast differentiation ( J:73663 )

• fail to develop normally

Genotype
MGI:5789537

ht3

• Allelic Composition: Csf1r^tm1Ers/Csf1r⁺
• Genetic Background: B6.129X1-Csf1r^tm1Ers

behavior/neurological

abnormal learning/memory/conditioning ( J:219294 )

• mice exhibit a lower preference for the novel (re-located) object compared with controls at 6-8 months of age, indicating impaired visuospatial memory

decreased coping response ( J:219294 )

♂ • males show increased depression-like behavior at 9-11 months of age, showing longer immobility times in the forced swim test

increased anxiety-related response ( J:219294 )

♂ • 9-11 month old males spend less time in the open arm of the elevate plus maze, indicating increased anxiety

ataxia ( J:219294 )

♀ • 2 females become ataxic at 8.5 and 11 months of age

impaired coordination ( J:219294 )

• 9-11, but not 6-8, month old mice show an increase in the number of slips on a narrow round balance beam

taste/olfaction

impaired olfaction ( J:219294 )

• 9-11 month old mice show increased latency to find buried food, indicating impaired olfaction

nervous system

increased oligodendrocyte progenitor number ( J:219294 )

• increase in PDGFRalpha+ oligodendrocyte precursors in layers II-III and V of the brain

microgliosis ( J:219294 )

• increase in microglial density throughout the brain

• gene expression analysis in adult brain suggests a proinflammatory microglia phenotype

abnormal lateral ventricle morphology ( J:219294 )

• increase in lateral ventricle volume in mice with severe sensorimotor dysfunction

enlarged lateral ventricles ( J:219294 )

• increase in left ventricle size in mice with severe sensorimotor dysfunction

abnormal brain white matter morphology ( J:219294 )

• cerebral white matter lesions in mice with severe sensorimotor dysfunction

abnormal corpus callosum morphology ( J:219294 )

• thinning of the corpus callosum in mice with severe sensorimotor dysfunction

neurodegeneration ( J:219294 )

• neuronal degeneration of white matter tracts

neuron degeneration ( J:219294 )

• a proportion of mature neurons in cortical layer V are lost between 11-weeks and 10-months of age

axonal spheroids ( J:219294 )

• presence of axonal spheroids in white matter tracts

demyelination ( J:219294 )

• increase in demyelinated axons in white matter tracts

hypermyelination ( J:219294 )

• presence of hypermyelinated axons in white matter tracts

hematopoietic system

microgliosis ( J:219294 )

• increase in microglial density throughout the brain

• gene expression analysis in adult brain suggests a proinflammatory microglia phenotype

immune system

microgliosis ( J:219294 )

• increase in microglial density throughout the brain

• gene expression analysis in adult brain suggests a proinflammatory microglia phenotype

cellular

increased oligodendrocyte progenitor number ( J:219294 )

• increase in PDGFRalpha+ oligodendrocyte precursors in layers II-III and V of the brain