B6;C3Fe a/a-Csf1^op/J

Stock number: 000231
Product name: osteopetrosis
Research areas: Cancer Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

Mice homozygous for the osteopetrosis spontaneous mutation (Csf1^op) may be useful to study the role of glia in neurological disease.

Detailed description

Mice homozygous for the osteopetrosis spontaneous mutation (Csf1^op) are viable and exhibit osteopetrosis. The osteoclasts are the primary cell type affected in homozygous mutant mice. This results in a generalized macrophage deficiency, monocytopenia, and defective bone remodeling. Homozygous mutant mice also have abnormal calcium regulation, impaired dental growth and female mice fail to lactate. Total leukocyte counts are reduced and marrow cells are decreased to one-tenth of normal control mice. Homozygous mutant mice have a deficient microglia and macrophage response, and therefore may be useful tools to study the role of glia in neurological disease if mated to transgenic models of neurodegenerative disease.
Homozygous pups are identifiable by their phenotype at 10 days of age by absence of incisors and by a domed skull. Unfortunately, ~50% of homozygotes die around weaning age. If they are to survive the weaning process, they must be provided with crushed food in the bottom of the cage. A soft rodent diet could also be used. Those that survive weaning may live up to 6 months.

Development

The osteopetrotic mutation (Csf1^op) arose spontaneously in 1970 at The Jackson Laboratory in the beginning congenic stock that became B6.DW-Pou1f1^dw/J, which was then at generation N3. Osteopetrotic heterozygotes were backcrossed to C57BL/6J for 7 generations. The line was then bred once to C3FeLe.B6-a/a/J and the strain was subsequently maintained via homozygous ovarian transplant host bred to (C57BL/6J x C3FeLe.B6-a/a/J)F1 then intercross of the obligate heterozygous offspring. Since 2010, The Jackson Laboratory live colony has been maintained by breeding mice heterozygous for Csf1^op to B6C3FeF1/J a/a mice (Stock No. 001022).

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
Molecular note: Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for a^t-2Gso and A^w-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039

Allele

Symbol: Csf1^op
Name: osteopetrosis
MGI accession ID: MGI:1856333
Generation method: Spontaneous
Marker symbol: Csf1
Marker name: colony stimulating factor 1 (macrophage)
Chromosome: 3
Strain of origin: B6;DW-Pou1f1^dw
Molecular note: A single nucleotide (T) insertion 262 bp downstream from the initiation codon resulted in a frameshift and the creation of a stop codon 21 bp downstream of the insertion.