The first four litters born to homozygous females should be fostered. BALB/cByJ (Stock No. 001026) or B6EiD2F1/J (Stock No. 003550) have been successfully used as foster mothers for this strain. This strain is homozygous for the retinal degeneration allele, Pde6brd1.
Wilson disease (WD) is an autosomal recessive defect of copper transport characterized by massive accumulation of copper in the liver, which can lead to liver failure. Mutations in a copper transporting ATPase (WND or ATP7B) have been shown to cause the disease. The toxic milk mouse mutant (Atb7b tx) accumulates copper in the liver in a manner similar to that observed in patients with WD. The autosomal recessive mutation (Atp7btx-J) arose in 1987 in the C3H/HeJ animal resources colony at The Jackson Laboratory. As with the Atb7b tx mutant, adult homozygous Atp7btx-J mice develop cirrhosis, and infant mice are pale colored, copper deficient, and display early mortality unless fostered by wild-type dams. The mutation comprises a G to A base substitution at position 2135 in exon 8 of the gene. This strain should be particularly useful in the study of neurological diseases in which copper accumulation plays an active role in pathology, including Alzheimer disease.
Toxic milk Jackson (Atp7btx-J) arose spontaneously in strain C3H/HeJ in 1988. One outcross was made to C3HeB/FeJ and then sibling matings were used to maintain the stock. The stock is maintained in the homozygous condition with the use of foster mothers.
|Allele Name||toxic milk Jackson|
|Gene Symbol and Name||Atp7b, ATPase, Cu++ transporting, beta polypeptide|
|Strain of Origin||C3H/HeJ|
|General Note||Tests at the University of Massachusetts proved its allelism to the original toxic milk mutation (J:28232).|
|Molecular Note||The mutation comprises a G to A base substitution at position 2135 in exon 8 of the gene. This is predicted to result in a Gly712Asp missense mutation in the second putative membrane-spanning domain of the encoded protein.|
Litters must be fostered prior to 14 days of age. On an agouti background, pups are dirty gray in coat color. On a non-agouti background, pups are bronze/copper in color. The first 4 litters will have all pups phenotypically dirty white and dead by 14 days due to the reduced copper concentration in the birth mother's milk. Pups can be fostered at up to 10-14 days of age, and survive, even from the first litter. The fifth litter and beyond may be phenotypically normal in coat color and live normally to survive to a year of age. These healthy progeny are still homozygous and their first 1 to 4 litters will be affected. At The Jackson Laboratory BALB/cByJ or B6EiD2F1 have been successfully used as foster mothers for this colony.
When using the toxic milk Jackson mouse strain in a publication, please cite the originating article(s) and include JAX stock #001576 in your Materials and Methods section.
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