Phenotypes associated with this allele

• Allele Symbol: Sqstm1^tm1Keta
• Allele Name: targeted mutation 1, Keiji Tanaka
• Allele ID: MGI:3774352
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sqstm1^tm1Keta/Sqstm1^tm1Keta	B6.129-Sqstm1^tm1Keta	MGI:5546008
hm2	Sqstm1^tm1Keta/Sqstm1^tm1Keta	involves: 129	MGI:3806621
hm3	Sqstm1^tm1Keta/Sqstm1^tm1Keta	involves: 129 * C57BL/6N	MGI:6387275
cn4	Atg7^tm1Tchi/Atg7^tm1Tchi Sqstm1^tm1Keta/Sqstm1^tm1Keta Tg(Mx1-cre)1Cgn/0	involves: 129 * C57BL/6 * C57BL/6NCrlj * CBA * CBA/JNCrlj	MGI:3806622
cn5	Atg7^tm1Tchi/Atg7^tm1Tchi Sqstm1^tm1Keta/Sqstm1^tm1Keta Tg(Nes-cre)1Wme/0	involves: 129 * C57BL/6 * C57BL/6NCrlj * CBA * CBA/JNCrlj	MGI:3806624

Genotype
MGI:5546008

hm1

• Allelic Composition: Sqstm1^tm1Keta/Sqstm1^tm1Keta
• Genetic Background: B6.129-Sqstm1^tm1Keta

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

growth/size/body

increased body weight ( J:201732 )

• similar in weight to littermates at birth but then gain weight much faster

behavior/neurological

increased food intake ( J:201732 )

• food intake increases linearly from 3.3 g/d/mouse at 5 weeks of age to 5.0 g/d/mouse at 50 weeks of age

• leptin treatment fails to inhibit food intake; however, responses to melanotan II and neuropeptide Y are similar to controls

homeostasis/metabolism

increased circulating leptin level ( J:201732 )

• increase is detectable at 3 weeks of age and continues to increase with age

impaired glucose tolerance ( J:201732 )

• in ad libitum fed mice

nervous system

increased neuron number ( J:201732 )

• increase in the number of neuropeptide Y neurons in young mice and gradually decreases with age

Genotype
MGI:3806621

hm2

• Allelic Composition: Sqstm1^tm1Keta/Sqstm1^tm1Keta
• Genetic Background: involves: 129

growth/size/body

increased susceptibility to age related obesity ( J:130839 )

• is observed in these mice

homeostasis/metabolism

hyperglycemia ( J:130839 )

• diabetes is observed in these mice

Genotype
MGI:6387275

hm3

• Allelic Composition: Sqstm1^tm1Keta/Sqstm1^tm1Keta
• Genetic Background: involves: 129 * C57BL/6N

growth/size/body

obese ( J:264183 )

• mice develop progressive obesity

skeleton

abnormal bone structure ( J:264183 )

• mice show an age-related Pagets disease of bone-like phenotype characterized by increased bone forming (increased trabecular network and serum PINP) and bone degrading activity (increased TRAP activity and serum CTX-I)

• Pagets disease of bone-like osteolytic lesions are seen at the diaphysis area in femora of 21-month old females

• adipocyte/lipid accumulation in the bones starts between 6-9 months in females, but is not seen in males

• however, levels of pro-inflammatory cytokines are not elevated

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

increased bone mineral density of femur ( J:264183 )

• femora maintain a relatively high bone density

increased bone volume ( J:264183 )

• bone volume fraction is higher in femora

abnormal trabecular bone morphology ( J:264183 )

• femora show elevated density of trabecular structures, especially at 9, 12, and 15 months of age

increased bone trabecula number ( J:264183 )

• increase in trabecular number in femora at 15 months of age, with differences in trabecular number starting to appear around 9 months of age

• however, trabecular thickness is not affected

decreased bone trabecular spacing ( J:264183 )

• decrease in trabecular separation in femora at 15 months of age, with differences in trabecular separation starting to appear around 9 months of age

abnormal bone remodeling ( J:264183 )

• femora maintain a relatively high bone density and thus a low trabecular separation during aging, indicating a transformation in bone turnover

• the increased trabecular bone structures and high bone-associated TRAP staining indicate increased bone turnover

abnormal osteoblast physiology ( J:264183 )

• high osteoblast activity at 21 months of age

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

cellular

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoblast physiology ( J:264183 )

• high osteoblast activity at 21 months of age

hematopoietic system

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

immune system

abnormal osteoclast differentiation ( J:264183 )

• bone marrow-derived monocytes grown in culture exhibit fast and premature in vitro osteoclastogenesis

abnormal osteoclast physiology ( J:264183 )

• high osteoclast activity at 21 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Paget's disease of bone		DOID:5408	OMIM:PS167250	J:264183

Genotype
MGI:3806622

cn4

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Sqstm1^tm1Keta/Sqstm1^tm1Keta; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6NCrlj * CBA * CBA/JNCrlj

homeostasis/metabolism

increased circulating alanine transaminase level ( J:130839 )

• slightly eleveated levels of ALT are found in the sera after Cre-induction but not to the degree of conditional knockouts with wild-type Sqstm1 alleles

increased circulating alkaline phosphatase level ( J:130839 )

• high levels of ALP are found in the sera after Cre-induction but not to the degree of conditional knockouts with wild-type Sqstm1 alleles

increased circulating aspartate transaminase level ( J:130839 )

• slightly elevated levels of AST are found in the sera after Cre-induction but not to the degree of conditional knockouts with wild-type Sqstm1 alleles

liver/biliary system

abnormal hepatocyte morphology ( J:130839 )

• the cytoplasmic inclusion bodies containing ubiquitinated proteins that are associated with Atg7 conditional liver knockout mice are almost completely absent in these mice

decreased liver function ( J:130839 )

• liver function is slightly decreased after Cre-induction but not to the degree of conditional knockouts with wild-type Sqstm1 alleles

Genotype
MGI:3806624

cn5

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Sqstm1^tm1Keta/Sqstm1^tm1Keta; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6NCrlj * CBA * CBA/JNCrlj

nervous system

absent hippocampus pyramidal cells ( J:130839 )

• large pyramidal neurons in the hippocampus are absent

absent cerebral cortex pyramidal cells ( J:130839 )

• large pyramidal neurons in the cerebral cortex are absent

decreased Purkinje cell number ( J:130839 )

• Purkinje cells in the cerebellum are absent in these mice

axon degeneration ( J:130839 )

• myelinated axons of the cerebellar nuclei are frequently enlarged and contain aberrant membranous structures and degenerated materials

abnormal nervous system physiology ( J:130839 )

• the cytoplasmic inclusion bodies containing ubiquitinated proteins that are found in the brain of Atg7 conditional knockouts are largely absent in these mice

increased neuron apoptosis ( J:130839 )

• increased apoptosis of the neurons occurs in the cerebellar nucleus and the cerebral cortex

behavior/neurological

limb grasping ( J:130839 )

• abnormal limb clasping is observed in mice

tremors ( J:130839 )

• is observed

cellular

increased neuron apoptosis ( J:130839 )

• increased apoptosis of the neurons occurs in the cerebellar nucleus and the cerebral cortex