Phenotypes associated with this allele

• Allele Symbol: Fzd9^tm1Uta
• Allele Name: targeted mutation 1, Uta Francke
• Allele ID: MGI:3526665
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fzd9^tm1Uta/Fzd9^tm1Uta	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:3578414
hm2	Fzd9^tm1Uta/Fzd9^tm1Uta	involves: 129X1/SvJ	MGI:4946080
ht3	Fzd9^tm1Uta/Fzd9^+	involves: 129X1/SvJ	MGI:4946081

Genotype
MGI:3578414

hm1

• Allelic Composition: Fzd9^tm1Uta/Fzd9^tm1Uta
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

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

mortality/aging

premature death ( J:98133 )

• exhibit moderately reduced lifespans

immune system

thymus atrophy ( J:98133 )

• exhibit accelerated atrophy with age

enlarged spleen ( J:98133 )

• spleens are approximately twice the normal size by 6 months of age

decreased pro-B cell number ( J:98133 )

• reduction in CD43+B220+ pro/pre-B-cell populations

decreased B cell number ( J:98133 )

• decreased total B-cell number in the bone marrow despite relatively normal numbers of mature B cells in the periphery

decreased pre-B cell number ( J:98133 )

• reduction in CD43+B220+ pro/pre-B-cell populations

increased leukocyte cell number ( J:98133 )

• older homozygous null mice have a high frequency of peripheral blood leukocytosis

increased eosinophil cell number ( J:98133 )

• older homozygous null mice exhibit eosinophilia

increased neutrophil cell number ( J:98133 )

• older homozygous null mice exhibit mild neutrophilia

increased monocyte cell number ( J:98133 )

• older homozygous null mice exhibit monocytosis

abnormal spleen red pulp morphology ( J:98133 )

• expansion of the red pulp with increased extramedullary hematopoiesis and deposition of increased amounts of hemosiderin

abnormal spleen marginal zone morphology ( J:98133 )

• although the white pulp is intact, there is some expansion of the marginal zones

abnormal lymph node morphology ( J:98133 )

• variably distorted nodal architecture

abnormal lymph node medullary cord morphology ( J:98133 )

• an accumulation of plasma cells that filled and distended the medullary cords and were present in large patches in the paracortical zones

enlarged lymph nodes ( J:98133 )

• lymph nodes are frequently enlarged, even at 3 months of age, with more than 50% of older homozygous null mice showing enlarged lymph nodes

hematopoietic system

thymus atrophy ( J:98133 )

• exhibit accelerated atrophy with age

enlarged spleen ( J:98133 )

• spleens are approximately twice the normal size by 6 months of age

decreased pro-B cell number ( J:98133 )

• reduction in CD43+B220+ pro/pre-B-cell populations

decreased B cell number ( J:98133 )

• decreased total B-cell number in the bone marrow despite relatively normal numbers of mature B cells in the periphery

decreased pre-B cell number ( J:98133 )

• reduction in CD43+B220+ pro/pre-B-cell populations

increased leukocyte cell number ( J:98133 )

• older homozygous null mice have a high frequency of peripheral blood leukocytosis

increased eosinophil cell number ( J:98133 )

• older homozygous null mice exhibit eosinophilia

increased neutrophil cell number ( J:98133 )

• older homozygous null mice exhibit mild neutrophilia

increased monocyte cell number ( J:98133 )

• older homozygous null mice exhibit monocytosis

abnormal spleen red pulp morphology ( J:98133 )

• expansion of the red pulp with increased extramedullary hematopoiesis and deposition of increased amounts of hemosiderin

abnormal spleen marginal zone morphology ( J:98133 )

• although the white pulp is intact, there is some expansion of the marginal zones

behavior/neurological

behavior/neurological phenotype ( J:98133 )

N • do not exhibit any neurological, reflex or behavioral problems or hyperacusis

endocrine/exocrine glands

thymus atrophy ( J:98133 )

• exhibit accelerated atrophy with age

growth/size/body

enlarged spleen ( J:98133 )

• spleens are approximately twice the normal size by 6 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Williams-Beuren syndrome	DOID:1928	OMIM:194050	J:98133

Genotype
MGI:4946080

hm2

• Allelic Composition: Fzd9^tm1Uta/Fzd9^tm1Uta
• Genetic Background: involves: 129X1/SvJ

skeleton

abnormal vertebral body morphology ( J:169924 )

• reduction in vertebral bodies by 35% and 40% at 24 and 52 weeks of age, respectively

decreased bone mineral density ( J:169924 )

• osteopenia

decreased bone volume ( J:169924 )

decreased compact bone thickness ( J:169924 )

• reduction in cortical thickness of femurs

decreased osteoblast cell number ( J:169924 )

• 30% reduction is osteoblast number

• however, no differences in osteoclast number

decreased bone trabecula number ( J:169924 )

abnormal skeleton development ( J:169924 )

impaired osteoblast differentiation ( J:169924 )

• osteoblastogenesis defect

abnormal skeleton physiology ( J:169924 )

decreased osteoblast proliferation ( J:169924 )

• calvaria-derived osteoblasts grown in culture in the presence of ascorbate and beta-glycerophosphate exhibit a decrease in proliferation at day 2 of differentiation

decreased bone mineralization ( J:169924 )

• isolated bone marrow cells grown in culture exhibit reduced mineralization after differentiation into osteoblasts but normal osteoclastogenesis

• calvaria-derived osteoblasts grown in culture for up to 20 days exhibit poor mineralization

decreased bone ossification ( J:169924 )

• 45% reduction in bone formation rate

decreased bone strength ( J:169924 )

• vertebral bodies and femora exhibit decreased biomechanical competence

cellular

impaired osteoblast differentiation ( J:169924 )

• osteoblastogenesis defect

decreased osteoblast proliferation ( J:169924 )

• calvaria-derived osteoblasts grown in culture in the presence of ascorbate and beta-glycerophosphate exhibit a decrease in proliferation at day 2 of differentiation

Genotype
MGI:4946081

ht3

• Allelic Composition: Fzd9^tm1Uta/Fzd9⁺
• Genetic Background: involves: 129X1/SvJ

skeleton

decreased bone mineral density ( J:169924 )

• osteopenia

decreased trabecular bone volume ( J:169924 )

decreased compact bone thickness ( J:169924 )

• reduction in cortical thickness of femurs

decreased osteoblast cell number ( J:169924 )

abnormal bone ossification ( J:169924 )

• decrease in bone rate formation

decreased bone strength ( J:169924 )

• vertebral bodies and femora exhibit decreased biomechanical competence

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Williams-Beuren syndrome		DOID:1928	OMIM:194050	J:169924