Phenotypes associated with this allele

• Allele Symbol: Runx3^tm1Yg
• Allele Name: targeted mutation 1, Yoram Groner
• Allele ID: MGI:2183399
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Runx3^tm1Yg/Runx3^tm1Yg	either: (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)	MGI:3652790
hm2	Runx3^tm1Yg/Runx3^tm1Yg	either: (involves: 129S1/Sv * 129X1/SvJ * ICR) or (involves: 129S1/Sv * 129X1/SvJ * MF1)	MGI:3057279
hm3	Runx3^tm1Yg/Runx3^tm1Yg	involves: 129S1/Sv * 129X1/SvJ	MGI:3652789
hm4	Runx3^tm1Yg/Runx3^tm1Yg	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:5689499
cx5	Runx2^tm1Mjo/Runx2^+ Runx3^tm1Yg/Runx3^tm1Yg	involves: 129S1/Sv * 129X1/SvJ * ICR	MGI:5689554

Genotype
MGI:3652790

hm1

• Allelic Composition: Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ * BALB/c) or (involves: 129S1/Sv * 129X1/SvJ * C57BL/6)

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

mortality/aging

postnatal lethality ( J:93240 )

• Background Sensitivity: increased compared to mice on an outbred MF-1 or ICR background

Genotype
MGI:3057279

hm2

• Allelic Composition: Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ * ICR) or (involves: 129S1/Sv * 129X1/SvJ * MF1)

Pathological findings in large intestines of Runx3^tm1Yg/Runx3^tm1Yg and +/+ wild-type.

mortality/aging

postnatal lethality, incomplete penetrance ( J:77764 , J:93240 )

• Background Sensitivity: mortality rate is increased on a 129 background compared to mice on outbred MF1 or ICR backgrounds (J:77764)

• Background Sensitivity: decreased compared to mice crossed onto a BALB/c or C57BL/6 background (J:93240)

behavior/neurological

abnormal eating behavior ( J:93240 )

• gastrointestinal tract contains little ingesta

ataxia ( J:77764 )

• severe limb ataxia and an uncoordinated gait

abnormal posture ( J:77764 )

• abnormal positioning of limbs when at rest

muscle

absent muscle spindles ( J:77764 )

• complete absence of spindles in many appendicular muscles, including the soleus, cranial tibial, and medial gastrocnemius; however a normal number of spindles are seen in the jaw-closing muscles and other head muscles

abnormal muscle tone ( J:77764 )

• frequent extensor rigidity in all four limbs

nervous system

absent muscle spindles ( J:77764 )

• complete absence of spindles in many appendicular muscles, including the soleus, cranial tibial, and medial gastrocnemius; however a normal number of spindles are seen in the jaw-closing muscles and other head muscles

abnormal sensory neuron morphology ( J:77764 )

• decreased expression of many proprioceptive neuron-specific markers while expression of markers of other neuron classes is similar to wild-type

abnormal sensory neuron innervation pattern ( J:77764 )

• complete loss of Ia afferent projections from the spinal gray matter at E16.5 and P0

small dorsal root ganglion ( J:77764 )

• overall volume is reduced by 32%, the total number of neurons is reduced by 26%, and the number of large diameter (greater then 20 um) neurons is reduced by 76%

abnormal dorsal spinal root morphology ( J:77764 )

• 44% reduction in the total number of myelinated axons in the dorsal root with a preferential loss of large diameter axons and a 62% reduction in dorsal root cross-sectional area at P30 - P35

• at P30 dorsal columns cross-sectional area is reduced by 39%

abnormal spinal cord dorsal horn morphology ( J:77764 )

• extends bilaterally closer to the midline than in wild-type mice; however the surface area of the cortico-spinal tract is unchanged

abnormal spinal cord dorsal column morphology ( J:77764 )

• at P30 dorsal column cross-sectional area is reduced by 39%

decreased spinal cord size ( J:77764 )

• 21% smaller

abnormal nervous system electrophysiology ( J:77764 )

• after stimulation of the L5 dorsal root afferents only a small short-latency ventral root potential and no short-latency monosynaptic reflex is seen in the L5 ventral root

• graded stimulation of L5 dorsal root afferents does not produce any significant short-latency postsynaptic potential

abnormal excitatory postsynaptic potential ( J:77764 )

• monosynaptic EPSPs are absent in 78% of motorneurons and when present have a very low amplitude

immune system

abnormal dendritic cell morphology ( J:88424 )

• increase in splenic CD8+ CD11b- and a decrease in CD8- CD11b+ dendritic cells

abnormal dendritic cell differentiation ( J:88424 )

• spontaneous and LPS-induced maturation of dendritic cells are significantly increased, while TGFB inhibition of maturation is absent

absent Langerhans cell ( J:88424 )

• absent from the skin; however the abundance of dendritic cells is similar to wild-type

increased dendritic cell number ( J:88424 , J:100348 )

• increase in the number of mature dendritic cells in bronchoalveolar lavages (J:88424)

• with or without LPS stimulation the proportion of CD11c+/CD11b+ alveolar dendritic cells is increased compared to wild-type mice (J:100348)

increased IgE level ( J:100348 )

• 3- and 4-fold increase in IgE in the serum and bronchoalveolar lavage, respectively

abnormal cytokine level ( J:93240 )

abnormal interferon level ( J:93240 )

• increase in the expression of IFNG in the colon of young and old mice

abnormal interleukin level ( J:93240 )

• increase in the expression of IL-12 and a slight increase in IL-4 and IL-10 expression in the colon of young and old mice

abnormal tumor necrosis factor level ( J:93240 )

• increase in expression in the colon of young and old mice

abnormal mesenteric lymph node morphology ( J:93240 )

• often enlarged and contain more cells

abnormal dendritic cell physiology ( J:88424 , J:100348 )

• increased ability to stimulate CD4+ T cell proliferation compared to wild-type cells (J:88424)

• up to 16% of dendritic cells in the thoracic lymph node express the high affinity receptor for IgE compared to only about 1% of cells in wild-type mice (J:100348)

• dendritic cells collected by bronchoalveolar lavage and derived from thoracic or axillary lymph nodes express higher levels of CCR7 (J:100348)

• TGFB fails to inhibit SLC/CCL21-mediated chemotaxis of bone marrow or dermal dendritic cells and CCR7-dependent migration of dendritic cells from the respiratory system into the draining lymph nodes is increased (J:100348)

abnormal inflammatory response ( J:93240 )

intestinal inflammation ( J:93240 )

colitis ( J:93240 )

• at 4 weeks of age colitis characterized by multifocal and coalescing mixed mucosal and submucosal infiltration of plasma cells, lymphocytes, histiocytes, and eosinophils is seen

• at the earliest stages, colits affects segments of the cecum and ascending and descending colon

• colitis occurs with equal severity when mice are housed in either specific pathogen free or conventional conditions

small intestinal inflammation ( J:93240 )

• seen in about 20% of mice

stomach inflammation ( J:93240 )

• mild multifocal mucosal and submucosal infiltrations of lymphocytes, plasma cells and eosinophils

lung inflammation ( J:88424 )

• at 8 weeks of age, 52% display prominent eosinophil infiltration in the lungs which also include mononuclear phagocytes and occasionally include lymphocytesin the interstitium around the blood vessels and airways

• vascular cuffs formed by eosinophils are seen

• in severe cases the infiltrate may expand into the alvolar septae and fill the alveolar spaces; however, inflammation is transient and is rarely seen in 2 to 6 month old mice at 8 - 11 weeks of age, bronchoalveolar lavage revealed increased eosinophils and increased levels of IL-5

• following exposure to sub-optimal doses of OVA, increased accumulation of dendritic cells is seen in bronchoalveolar lavages

respiratory system

abnormal lung epithelium morphology ( J:88424 )

• inflammation may be accompanied by airway epithelial hyperplasia

abnormal respiratory system physiology ( J:88424 )

• inflammation may be accompanied by mucus hypersecretion and excess collagen deposition

lung inflammation ( J:88424 )

• at 8 weeks of age, 52% display prominent eosinophil infiltration in the lungs which also include mononuclear phagocytes and occasionally include lymphocytesin the interstitium around the blood vessels and airways

• vascular cuffs formed by eosinophils are seen

• in severe cases the infiltrate may expand into the alvolar septae and fill the alveolar spaces; however, inflammation is transient and is rarely seen in 2 to 6 month old mice at 8 - 11 weeks of age, bronchoalveolar lavage revealed increased eosinophils and increased levels of IL-5

• following exposure to sub-optimal doses of OVA, increased accumulation of dendritic cells is seen in bronchoalveolar lavages

increased airway responsiveness ( J:100348 )

• at 4 to 9 weeks of age, increased airway responsiveness to doses of methacholine from 40 mg/ml to 200 mg/ml is seen, with suffocation of mutants but not wild-type mice seen with exposure to 200 mg/ml

• by 5 - 6 months of age airway responsiveness is similar to wild-type

digestive/alimentary system

abnormal crypts of Lieberkuhn morphology ( J:93240 )

• crypt loss often accompanies colitis

abnormal large intestine morphology ( J:93240 )

• mucosal hyperplasia often accompanies colitis

• fibrosis of the lamina propria sometimes accompanies colitis

abnormal cecum morphology ( J:93240 )

• cecal wall is frequently thickened, rigid and opaque

abnormal colon morphology ( J:93240 )

• variable tubular thickening

abnormal stomach mucosa morphology ( J:93240 )

• mice older than 8 months develop progressive hyperplasia of the gastric glandular mucosa beginning in the pyloric region and eventually involving the entire glandular stomach wall

• hyperplatic mucosa displays disturbed epithelial differentiation, elongation of the gastric pits and glands, and prominent hyaline degeneration in which the cytoplasm of the epithelial cells expands and becomes smooth and hypereosinophilic

• in advanced cases the hyperplastic mucosa protrudes into the adjacent layers but not through the serosa; however gastric neoplasms with the exception of isolated mucosal polyps, are not detected

abnormal gastric chief cell morphology ( J:93240 )

• lost in severe cases of gastric glandular mucosal hyperplasia

abnormal gastric parietal cell morphology ( J:93240 )

• lost in severe cases of gastric glandular mucosal hyperplasia

abnormal digestive system physiology ( J:93240 )

• the overall stomach lesion is consistent with proliferative gastritis

intestinal inflammation ( J:93240 )

colitis ( J:93240 )

• at 4 weeks of age colitis characterized by multifocal and coalescing mixed mucosal and submucosal infiltration of plasma cells, lymphocytes, histiocytes, and eosinophils is seen

• at the earliest stages, colits affects segments of the cecum and ascending and descending colon

• colitis occurs with equal severity when mice are housed in either specific pathogen free or conventional conditions

small intestinal inflammation ( J:93240 )

• seen in about 20% of mice

stomach inflammation ( J:93240 )

• mild multifocal mucosal and submucosal infiltrations of lymphocytes, plasma cells and eosinophils

skeleton

lordosis ( J:77764 )

• resulting from frequent extensor rigidity in all four limbs

growth/size/body

decreased body size ( J:77764 )

decreased body weight ( J:93240 )

• reduced to about 50% of wild-type

adipose tissue

decreased total body fat amount ( J:93240 )

• minimal fat stores

hematopoietic system

abnormal dendritic cell morphology ( J:88424 )

• increase in splenic CD8+ CD11b- and a decrease in CD8- CD11b+ dendritic cells

abnormal dendritic cell differentiation ( J:88424 )

• spontaneous and LPS-induced maturation of dendritic cells are significantly increased, while TGFB inhibition of maturation is absent

absent Langerhans cell ( J:88424 )

• absent from the skin; however the abundance of dendritic cells is similar to wild-type

increased dendritic cell number ( J:88424 , J:100348 )

• increase in the number of mature dendritic cells in bronchoalveolar lavages (J:88424)

• with or without LPS stimulation the proportion of CD11c+/CD11b+ alveolar dendritic cells is increased compared to wild-type mice (J:100348)

increased IgE level ( J:100348 )

• 3- and 4-fold increase in IgE in the serum and bronchoalveolar lavage, respectively

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:93240 )

• crypt loss often accompanies colitis

abnormal gastric chief cell morphology ( J:93240 )

• lost in severe cases of gastric glandular mucosal hyperplasia

abnormal gastric parietal cell morphology ( J:93240 )

• lost in severe cases of gastric glandular mucosal hyperplasia

homeostasis/metabolism

abnormal cytokine level ( J:93240 )

abnormal interferon level ( J:93240 )

• increase in the expression of IFNG in the colon of young and old mice

abnormal interleukin level ( J:93240 )

• increase in the expression of IL-12 and a slight increase in IL-4 and IL-10 expression in the colon of young and old mice

abnormal tumor necrosis factor level ( J:93240 )

• increase in expression in the colon of young and old mice

integument

abnormal auchene hair morphology ( J:99572 )

• shorter with less prominent bends

sparse hair ( J:99572 )

• appears less dense with more prominent outer guard hairs

abnormal zigzag hair morphology ( J:99572 )

• constitute only 55% of the total hair compared to about 70% in wild-type

• shorter with fewer (2 compared to 3 to 5 in wild-type) and less prominent bends

• the bend regions appear thicker, large regions where the air cells seem more refractive to light are present, and the hairs seem less flexible

cellular

abnormal dendritic cell differentiation ( J:88424 )

• spontaneous and LPS-induced maturation of dendritic cells are significantly increased, while TGFB inhibition of maturation is absent

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
asthma		DOID:2841	OMIM:600807	J:100348
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:93240

Genotype
MGI:3652789

hm3

• Allelic Composition: Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

postnatal lethality ( J:77764 )

• Background Sensitivity: mortality rate is increased on a 129 background compared to mice on outbred MF1 or ICR backgrounds

behavior/neurological

ataxia ( J:77764 )

• severe limb ataxia and an uncoordinated gait

abnormal posture ( J:77764 )

• abnormal positioning of limbs when at rest

muscle

abnormal muscle tone ( J:77764 )

• frequent extensor rigidity in all four limbs

skeleton

lordosis ( J:77764 )

• resulting from frequent extensor rigidity in all four limbs

immune system

abnormal CD8-positive, alpha beta T cell morphology ( J:109584 )

• marked increase in the number of mature CD8+ cells that abnormally express CD4 is seen in the thymus and spleen

• less than 10% of CD8+ splenocytes express Itgae compared to over 90% in wild-type mice

growth/size/body

decreased body size ( J:77764 )

hematopoietic system

abnormal CD8-positive, alpha beta T cell morphology ( J:109584 )

• marked increase in the number of mature CD8+ cells that abnormally express CD4 is seen in the thymus and spleen

• less than 10% of CD8+ splenocytes express Itgae compared to over 90% in wild-type mice

Genotype
MGI:5689499

hm4

• Allelic Composition: Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

behavior/neurological

ataxia ( J:243559 )

• severe

abnormal gait ( J:243559 )

• severely impaired gait pattern

• posterior placement of forelimbs and uncoordinated limb placement

• at 3 months of age gait regularity is substantially decreased

cellular

decreased osteoblast proliferation ( J:224290 )

• more than 50% reduction in the number of BrdU+ cells in calvarial sections of newborns indicating decreased proliferation of osteoblast progenitor cells

• cultured osteoblasts show impaired proliferation and bone matrix formation

muscle

decreased skeletal muscle fiber size ( J:243559 )

• decrease in mean fiber area in the muscles attached to the spine

• however, no left vs right side differences are seen

growth/size/body

decreased body size ( J:224290 )

• dwarfism

skeleton

skeleton phenotype ( J:243559 )

N • developing spines show no gross abnormalities

decreased osteoblast proliferation ( J:224290 )

• more than 50% reduction in the number of BrdU+ cells in calvarial sections of newborns indicating decreased proliferation of osteoblast progenitor cells

• cultured osteoblasts show impaired proliferation and bone matrix formation

abnormal skeleton morphology ( J:224290 )

• small skeleton

• bones show 41% and 34% decreases in thickness and total section area, respectively, at 3 weeks of age

abnormal cranium morphology ( J:224290 )

• the intramembranous skull bones are softer than in wild-type mice at E18.5

• diminution of bone tissue in skulls

small neurocranium ( J:224290 )

• calvaria are reduced in size

decreased diameter of femur ( J:224290 )

• reduction in femoral width, with a 50% smaller bone cortex area than wild-type mice at 3 weeks of age

abnormal clavicle morphology ( J:224290 )

• clavicles are softer than in wild-type mice at E18.5

decreased length of long bones ( J:224290 )

• short long bones in 3 week old mice

short humerus ( J:224290 )

• humeri are 15% shorter at 1 day of age

short femur ( J:224290 )

• femurs are 19% shorter in 3 week old mice

kyphosis ( J:224290 )

• in 5 month old mice

scoliosis ( J:243559 )

• 19 of 20 mice show scoliosis at P90 with a curve range between 12 and 71 degrees

• most commonly this is seen as a major thoracic curve accompanied by smaller curves rostrally and caudally

• in 16 of 19 mice the apex of the major curve is right-sided and located between spinal levels T8 and T10

• curvature is seen in only a single mouse at P40 but is present by P60

• curvature worsens between P60 and P90 and more slowly after P90

• bend is to the right of the coronal plane

decreased bone mineral content ( J:224290 )

• cortices of 3 week old mice show a 58% reduction in bone mineral content

• 59% decrease in trabecular bone mineral content at 3 weeks of age

decreased bone mineral density ( J:224290 )

• cortices of 3 week old mice show osteopenia, including 14% and 58% reductions in bone mineral density and bone mineral content, respectively

• osteopenia is congenital, with delayed ossification seen at E14.5

decreased bone mineral density of femur ( J:224290 )

• osteopenia is seen in the cancellous region of the femur, with a decrease in trabecular bone mineral density (28%) and trabecular bone mineral content (59%) compared to wild-type mice at 3 weeks of age

decreased bone volume ( J:224290 )

decreased compact bone thickness ( J:224290 )

• long bones show reduced cortical thickness at 3 weeks of age

decreased osteoblast cell number ( J:224290 )

• 38% and 34% reduction in the surface osteoblast/bone surface ratio and in the number of osteoblasts/bone perimeter, respectively, indicating reduced osteoblast numbers

• however, osteoclast numbers are normal

abnormal trabecular bone morphology ( J:224290 )

• long bones show underdeveloped trabecular regions at 3 weeks of age

decreased trabecular bone volume ( J:224290 )

decreased trabecular bone thickness ( J:224290 )

• osteopenia is also seen in the cancellous region of the femur, with decreases in trabecular thickness (22%), trabecular bone mineral density (28%), and trabecular bone mineral content (59%) compared to wild-type mice at 3 weeks of age

decreased bone mass ( J:224290 )

• lower bone mass, with a 38% decrease in bone volume/total volume

abnormal skeleton development ( J:224290 )

• complete lack of bone material is seen at E14.5, the earliest time point of bone appearance, compared to wild-type which show bulk calcification in the bone collar and primary spongiosa regions, however, mineral deposits are seen at E16.5, indicating delayed osteogenesis which commences by around E16.5

abnormal bone mineralization ( J:224290 )

• 19% decrease in the mineral apposition rate and a reduction of the mineralizing surface/bone surface and the bone formation rate of 59% and 68%, respectively

• mice show diminished mineralization of intramembranous bones

abnormal intramembranous bone ossification ( J:224290 )

• perinatal intramembranous ossification deficits

delayed bone ossification ( J:224290 )

• E18.5 mutants show delayed ossification of the hind- and forelimb distal bones, the mandible (angular process), and skull and is seen as early as E16.5

• by 7 days of age, mice show a normal ossification pattern even though the skeleton is smaller

decreased bone stiffness ( J:224290 )

• decrease in bone rigidity, with mice showing a 33% reduction in Youngs modulus, a size-corrected measure of bone material rigidity

decreased bone strength ( J:224290 )

• bone strength of intramembranous bones (frontal bones and clavicles) are reduced

limbs/digits/tail

short humerus ( J:224290 )

• humeri are 15% shorter at 1 day of age

decreased diameter of femur ( J:224290 )

• reduction in femoral width, with a 50% smaller bone cortex area than wild-type mice at 3 weeks of age

short femur ( J:224290 )

• femurs are 19% shorter in 3 week old mice

craniofacial

abnormal cranium morphology ( J:224290 )

• the intramembranous skull bones are softer than in wild-type mice at E18.5

• diminution of bone tissue in skulls

small neurocranium ( J:224290 )

• calvaria are reduced in size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
idiopathic scoliosis		DOID:0060250		J:243559

Genotype
MGI:5689554

cx5

• Allelic Composition: Runx2^tm1Mjo/Runx2⁺; Runx3^tm1Yg/Runx3^tm1Yg
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * ICR

mortality/aging

postnatal lethality, incomplete penetrance ( J:224290 )

• only a few mice survive to 1 week of age

skeleton

delayed bone ossification ( J:224290 )

• digital bones of 0.5 day old mice remain grossly cartilaginous indicating delayed skeletal ossification