B6;129-Ctsb^tm1Jde/J

Stock number: 030971
Product name: Cat B^-
Strain synonyms: CTSB KO
Research areas: Developmental Biology Research, Neurobiology Research

Description

In Ctsb KO mice, loss of CTSB alters the exercise-dependent increase in hippocampal neurogenesis and improved spatial memory found in wild-type mice. These mice may be useful for studying the relationship between exercise and brain function.

Detailed description

CTSB (cathepsin B or Cat B) is a member of the C1 family of peptidases and functions as a lysosomal cysteine protease with both endopeptidase and exopeptidase activity. Although cathepsin B is ubiquitously expressed throughout the body, it is also myokine secreted by muscle during exercise. CTSB levels in mouse gastrocnemius muscle and plasma are increased during exercise; a similar increase is seen in plasma from both human and Rhesus monkeys. These knock-out mice contain a neomycin cassette inserted into exon 4. Homozygous knock-out mice exhibit increased immobility time in forced swim test, a decreased frequency of miniature inhibitory post-synaptic currents (mIPSCs) and a more depolarized resting membrane potential in dentate granule cells and a decrease in hippocampal P11. In wild-type mice, running improves spatial memory and increases hippocampal neurogenesis; loss of CTSB in knock-out mice abrogates the beneficial effects of exercise on the brain. Mice homozygous for the mutation are viable and fertile. These mice may be useful for studying the relationship between exercise and brain function.

Development

The targeting vector contains a neomycin cassette inserted into exon 4. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 and 129/Sv females. Offspring were maintained on the segregating background. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Allele

Symbol: Ctsb^tm1Jde
Name: targeted mutation 1, Jan Deussing
MGI accession ID: MGI:2182129
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Cat B^-; CathB^-; Ctsb^-
Marker symbol: Ctsb
Marker name: cathepsin B
Marker synonyms: APPS; CB; CPSB; KWE; RECEUP
Chromosome: 14
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin selection cassette was inserted into a BglII site in exon 4. Northern blot analysis of total RNA showed a lack of transcript in homozygous mutant mice. An absence of protein in homozygous mutant mice was determined by Western blot analysis of kidney lysosomal protein extracts. The proteolytic activity of the endogenous protein was found to be absent using an assay involving liver lysosomal extracts obtained from of homozygous mutant mice and a fluorogenic substrate.
General note: in combination with Ctsl^tm1Cptr, double homozygous mutant have some similarities but distinct phenotypic characteristics compared to the human syndrome: neuronal ceroid lipofuscinoses (NLCs)