B6.129(Cg)-Cln3^tm1.1Mem/J

Stock number: 017895
Product name: Cln3deltaex7/8
Research areas: Neurobiology Research, Research Tools, Sensorineural Research

Description

These Cln3^Δex7/8 knock in mice exhibit sensorimotor deficits, retinal degeneration, metabolic, hematological abnormalities, and accumulate mitochondrial ATPase subunit c, and may be useful in studies of juvenile onset neuronal ceroid lipofuscinosis (JNCL), also known as Batten or Spielmeyer-Vogt disease.

Detailed description

These mice carry a 1.02kb deletion mutation that recapitulates the most common mutation (>80%) found in juvenile-onset neuronal ceroid lipofuscinosis (JNCL) patients. Mice that are homozygous for the targeted mutation on the C57BL/6 background are viable and fertile. Northern blot and RT PCR analyses of kidney, liver and brain tissue from homozygotes detect mutant mRNA. Truncated polypeptide and non-truncated alternatively spliced gene products are present. Autofluorescent lysosomal material containing immunoreactive ATPase subunit c are found in the brain and heart. Homozygous mice on the C57BL/6N background exhibit progressive retinal degeneration starting at 20 weeks of age. At 10-14 weeks of age homozygotes display slight deficits in sensory and motor tasks. Increased rectal body temperature and minimum oxygen consumption are observed in homozygotes 12-13 weeks of age. The heart weight of 20 week old homozygotes is slightly increased, although cardiac function is normal in young adults. At 15-16 weeks of age homozygotes on the C57BL/6N background exhibit exhibit elevated serum ferritin levels, mean red blood cell corpuscular volume, and reticulocyte numbers. Homozygotes have vacuolated peripheral blood lymphocytes (observed as early as the neonatal period), and male homozygotes exhibit vacuolation in epididymal clear cells.

Development

A targeting vector containing a loxP site flanked PGKneo cassette was used to disrupt exons 7 and 8 and adjacent non-coding sequence of the targeted gene. The construct was electroporated into 129-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting line was then bred to a CMV-cre transgenic strain to remove the neo cassette from the targeted allele. The mice have been bred to 129SvEv and CD1 backgrounds. The mice were then backcrossed to C57BL/6J (Stock No. 000664)for 11 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Cln3^tm1.1Mem
Name: targeted mutation 1.1, Marcy MacDonald
MGI accession ID: MGI:2388888
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cln3
Marker name: ceroid lipofuscinosis, neuronal 3, juvenile (Batten, Spielmeyer-Vogt disease)
Chromosome: 7
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: A floxed neo cassette that had replaced exons 7 and 8 was excised from Cln3^tm1Mem via in vivo cre mediated recombination in the germline. Expression analyses showed the presence of various aberrantly splice transcripts. Translation of a cDNA derived from RT-PCR analysis produced a protein containing the amino and carboxyl terminals as well as a novel mid-section. BLASTN revealed homology with a protein isolated from a patient with the juvenile-onset form of neuronal ceroid lipofuscinosis (JNCL).