Phenotypes associated with this allele

• Allele Symbol: Clcn7⁺
• Allele Name: wild type
• Allele ID: MGI:2438271
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Clcn7^tm1.1Mjec/Clcn7^+	involves: 129 * 129S/SvEv * C57BL/6	MGI:5563125
ht2	Clcn7^tm5.1Tjj/Clcn7^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6267452
ht3	Clcn7^tm4.1Tjj/Clcn7^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4459534
ht4	Clcn7^tm1.1Teti/Clcn7^+	involves: 129S2/SvPas * C57BL/6	MGI:5563098
ht5	Clcn7^tm1.1Mjec/Clcn7^+	involves: 129S/SvEv * BALB/cJ * C57BL/6	MGI:5563152
ht6	Clcn7^tm1.1Mjec/Clcn7^+	involves: 129S/SvEv * C57BL/6 * DBA/2J	MGI:5563141
ht7	Clcn7^tm1.1Mawa/Clcn7^+	involves: C57BL/6J * C57BL/6N * CD-1	MGI:6259526

Genotype
MGI:5563125

ht1

• Allelic Composition: Clcn7^tm1.1Mjec/Clcn7⁺
• Genetic Background: involves: 129 * 129S/SvEv * C57BL/6

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

skeleton

increased areal bone mineral density ( J:203761 )

• whole areal bone mineral density at 3 months of age is very high

• Background Sensitivity: 8% increase in whole body areal bone mineral density on the 129 background compared to 4% increase on a DBA/2J background and 3.8% on a BALB/cJ background

increased trabecular bone volume ( J:203761 )

increased bone trabecula number ( J:203761 )

decreased bone trabecular spacing ( J:203761 )

• trabecular separation is lower

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant osteopetrosis 2		DOID:0110938	OMIM:166600	J:203761

Genotype
MGI:6267452

ht2

• Allelic Composition: Clcn7^tm5.1Tjj/Clcn7⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

normal phenotype

no abnormal phenotype detected ( J:217031 )

• mice lack an obvious phenotype

Genotype
MGI:4459534

ht3

• Allelic Composition: Clcn7^tm4.1Tjj/Clcn7⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

hippocampal neuron degeneration ( J:160702 )

• after 5 months, mice exhibit hippocampal degeneration with features of lysosomal disease unlike wild-type mice

vision/eye

retina degeneration ( J:160702 )

Genotype
MGI:5563098

ht4

• Allelic Composition: Clcn7^tm1.1Teti/Clcn7⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

hematopoietic system

increased osteoclast cell number ( J:203761 )

• increase in osteoclast number at 3 months of age

• increase in osteoclast surface/bone surface ratio in the proximal tibia at 3 months of age

• when cultured with M-CSF and RANKL, TRAcP-positive mononuclear osteoclast precursors from the bone marrow form a higher number of osteoclasts

abnormal osteoclast physiology ( J:203761 )

• osteoclasts show a reduction of resorption pit formation

homeostasis/metabolism

increased circulating parathyroid hormone level ( J:203761 )

immune system

increased osteoclast cell number ( J:203761 )

• increase in osteoclast number at 3 months of age

• increase in osteoclast surface/bone surface ratio in the proximal tibia at 3 months of age

• when cultured with M-CSF and RANKL, TRAcP-positive mononuclear osteoclast precursors from the bone marrow form a higher number of osteoclasts

abnormal osteoclast physiology ( J:203761 )

• osteoclasts show a reduction of resorption pit formation

nervous system

nervous system phenotype ( J:203761 )

N • mice do not exhibit neurodegeneration in the hippocampus or cerebellar cortex at 1 or 12 months of age

skeleton

increased osteoclast cell number ( J:203761 )

• increase in osteoclast number at 3 months of age

• increase in osteoclast surface/bone surface ratio in the proximal tibia at 3 months of age

• when cultured with M-CSF and RANKL, TRAcP-positive mononuclear osteoclast precursors from the bone marrow form a higher number of osteoclasts

abnormal osteoclast physiology ( J:203761 )

• osteoclasts show a reduction of resorption pit formation

abnormal bone marrow morphology ( J:203761 )

• bone marrow shows increased TRAcP-positive mononuclear osteoclast precursors; when cultured with M-CSF and RANKL, these precursors form a higher number of osteoclasts

increased areal bone mineral density ( J:203761 )

• 3 month old mice have a higher whole body areal bone mineral density

increased trabecular bone volume ( J:203761 )

• 3 month old mice exhibit a greater trabecular bone volume in femur, tibia, and vertebrae

increased bone trabecula number ( J:203761 )

• in 3 month old mice

decreased bone trabecular spacing ( J:203761 )

• 3 month old mice exhibit a lesser trabecular separation

• however, no changes in trabecular thickness are seen

increased bone mass ( J:203761 )

• increase in bone mass is persistent with time

• females have a lower bone mass and more pronounced bone volume/total tissue volume elevation than males

osteopetrosis ( J:203761 )

• exhibit signs of milder osteopetrosis

decreased bone resorption ( J:203761 )

• marker analysis suggests a reduction of bone resorption

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant osteopetrosis 2		DOID:0110938	OMIM:166600	J:203761

Genotype
MGI:5563152

ht5

• Allelic Composition: Clcn7^tm1.1Mjec/Clcn7⁺
• Genetic Background: involves: 129S/SvEv * BALB/cJ * C57BL/6

skeleton

increased bone mineral density ( J:203761 )

• Background Sensitivity: 3.8% increase in whole body areal bone mineral density on the BALB/cJ background compared to 8% increase on a 129 background and 4% on a DBA/2J background

increased trabecular bone volume ( J:203761 )

Genotype
MGI:5563141

ht6

• Allelic Composition: Clcn7^tm1.1Mjec/Clcn7⁺
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA/2J

homeostasis/metabolism

increased circulating alkaline phosphatase level ( J:203761 )

skeleton

increased bone mineral density ( J:203761 )

• Background Sensitivity: 4% increase in whole body areal bone mineral density on the DBA/2J background compared to 8% increase on a 129 background and 3.8% on a BALB/cJ background

abnormal trabecular bone morphology ( J:203761 )

• trabecular separation is lower

increased trabecular bone volume ( J:203761 )

increased bone trabecula number ( J:203761 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant osteopetrosis 2		DOID:0110938	OMIM:166600	J:203761

Genotype
MGI:6259526

ht7

• Allelic Composition: Clcn7^tm1.1Mawa/Clcn7⁺
• Genetic Background: involves: C57BL/6J * C57BL/6N * CD-1

skeleton

increased osteoclast cell number ( J:254787 )

♂ • males exhibit more osteoclasts per bone perimeter and surface area indicating increased osteoclast number

♂ • interferon-gamma therapy decreases osteoclast number

increased bone mineral density ( J:254787 )

♂ • males show a slight increase in bone mineral density at 12 weeks of age

increased trabecular bone volume ( J:254787 )

• mice exhibit an increase in trabecular bone volume fraction

• interferon-gamma therapy from 4-12 weeks of age does not reduce trabecular bone volume

decreased compact bone area ( J:254787 )

♂ • males exhibit a decrease in cortical area fraction

decreased compact bone thickness ( J:254787 )

♂ • males exhibit a decrease in cortical thickness

increased bone trabecula number ( J:254787 )

decreased bone trabecular spacing ( J:254787 )

increased trabecular bone thickness ( J:254787 )

♀ • females exhibit an increase in trabecular thickness

osteopetrosis ( J:254787 )

decreased bone strength ( J:254787 )

♂ • males, but not females, show a decrease in energy to ultimate force in the three-point bending assay, indicating decreased bone strength

hematopoietic system

increased osteoclast cell number ( J:254787 )

♂ • males exhibit more osteoclasts per bone perimeter and surface area indicating increased osteoclast number

♂ • interferon-gamma therapy decreases osteoclast number

immune system

increased osteoclast cell number ( J:254787 )

♂ • males exhibit more osteoclasts per bone perimeter and surface area indicating increased osteoclast number

♂ • interferon-gamma therapy decreases osteoclast number

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal dominant osteopetrosis 2		DOID:0110938	OMIM:166600	J:254787