Phenotypes associated with this allele

• Allele Symbol: Clcn7^tm4.1Tjj
• Allele Name: targeted mutation 4.1, Thomas J Jentsch
• Allele ID: MGI:4459519
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Clcn7^tm4.1Tjj/Clcn7^tm4.1Tjj	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4459532
ht2	Clcn7^tm4.1Tjj/Clcn7^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4459534

Genotype
MGI:4459532

hm1

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

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

mortality/aging

premature death ( J:160702 )

• mice die within 5 weeks of age

growth/size/body

abnormal tooth eruption ( J:160702 )

• impaired

decreased body weight ( J:160702 )

postnatal growth retardation ( J:160702 )

craniofacial

small cranium ( J:160702 )

abnormal tooth eruption ( J:160702 )

• impaired

skeleton

small cranium ( J:160702 )

abnormal tooth eruption ( J:160702 )

• impaired

abnormal osteoclast morphology ( J:160702 , J:217031 )

• the acid-secreting membrane of osteoclasts are underdeveloped compared with wild-type cells (J:160702)

• all osteoclasts form ruffled border membranes, of which 70% appear mature (J:217031)

abnormal osteoclast physiology ( J:160702 )

• osteoclast excavated pits are decreased in number and depths compared to in wild-type mice

increased bone mineral density ( J:160702 )

• trabecular bone density is increased compared to in wild-type mice

abnormal trabecular bone morphology ( J:160702 )

• mice exhibit increased bone volume fraction, trabecular thickness, and trabecular number while trabecular separation is decreased compared with wild-type mice

increased trabecular bone thickness ( J:160702 )

osteopetrosis ( J:160702 , J:217031 )

• not as severe as in null mice (J:160702)

• mice exhibit a less severe osteopetrosis (of tibiae) than null mice or Clcn7^tm5.1Tjj homozygotes (J:217031)

nervous system

neurodegeneration ( J:160702 )

• severe

cellular

abnormal autophagy ( J:217031 )

• at 3 weeks of age, the autophagic marker LC3-II is significantly increased in the brain, unlike in wild-type controls or Clcn7^tm5.1Tjj homozygotes

abnormal lysosome physiology ( J:160702 )

• lysosomes are more alkaline than lysosomes from null mice but not as much as lysosomes from wild-type

vision/eye

retina degeneration ( J:160702 , J:217031 )

• at 4 weeks of age, mice exhibit degeneration of photoreceptor cells in the outer nuclear layer (ONL) and outer and inner segment, unlike in wild-type controls or Clcn7^tm5.1Tjj homozygotes (J:217031)

homeostasis/metabolism

abnormal autophagy ( J:217031 )

• at 3 weeks of age, the autophagic marker LC3-II is significantly increased in the brain, unlike in wild-type controls or Clcn7^tm5.1Tjj homozygotes

hematopoietic system

abnormal osteoclast morphology ( J:160702 , J:217031 )

• the acid-secreting membrane of osteoclasts are underdeveloped compared with wild-type cells (J:160702)

• all osteoclasts form ruffled border membranes, of which 70% appear mature (J:217031)

abnormal osteoclast physiology ( J:160702 )

• osteoclast excavated pits are decreased in number and depths compared to in wild-type mice

immune system

abnormal osteoclast morphology ( J:160702 , J:217031 )

• the acid-secreting membrane of osteoclasts are underdeveloped compared with wild-type cells (J:160702)

• all osteoclasts form ruffled border membranes, of which 70% appear mature (J:217031)

abnormal osteoclast physiology ( J:160702 )

• osteoclast excavated pits are decreased in number and depths compared to in wild-type mice

pigmentation

pigmentation phenotype ( J:160702 , J:217031 )

N • unlike null mice, coat color is brownish (J:160702)

N • surprisingly, mice display brown fur on an agouti background; hair shaft pigmentation is unchanged relative to that in wild-type controls (J:217031)

Genotype
MGI:4459534

ht2

• 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 )