This inbred strain carries the spontaneous flexed-tail mutation and mice are characterized by a transitory siderocytic hypochromic anemia due to defective heme synthesis in fetal but not adult reticulocytes. Belly spots and tail flexures are common.Read More +
See article "Genetic Background Effects: Can Your Mice See?", JAX® NOTES Spring 2002, No. 485.
Flexed tail homozygotes can be identified hematologically as earlyas embryonic day 13 and are detectably paler than normal by embryonic day 16, with most paler than normal by embryonic day 15. Homozygotes are small at birth and have a transitory siderocytic hypochromic anemia due to defective heme synthesis in fetal but not adult reticulocytes. Fetal erythrocytes have more alpha hemoglobin synthesis than beta hemoglobin synthesis. Very high numbers of siderocytes are found at birth and this decreases during the first few weeks of life and stabilizes at approximately 3 weeks of age with 3% siderocytes, significantly higher than in wildtype adults. Most homozygotes have a belly spot and 1 to 5 flexures in the tail due to vertebral fusions. Vertebral fusions are also found elsewhere in the vertebral column. Fewer than expected homozygotes are generated indicating prenatal death and the postnatal death rate is approximately 4 times normal. A small minority of homozygotes have been found to have embryonic neural tube defects or a dorsal enlargement of the head.
In 2019-2020, researchers at The Jackson Laboratory discovered this inbred strain contains the Trem2S148E allele - a naturally occurring variant at position 48351151-48351152 on Chr 17 (rs108080490 and rs107649577; Ensembl GRCm38.p6). This TC to GA transition results in a serine to glutamic acid substitution at amino acid 148 (S148E).
The FL/1Re inbred strain, homozygous for f and wildtype for Kit, was generated in the laboratory of Elizabeth Russell from a female WB/Re heterozygous for KitW bred to a male heterozygous for f from a partially inbred stock derived from crosses between C3H/J and Snell?s WA linkage-testing stock (Russell and McFarland, 1966). This strain reached generation F60 in 1974, and in 1979 embryos were generated for cryopreservation from homozygous (f/f) females and males at generation F78. This bankstock was thawed and replenished with F82p embryos in 1996.
|Allele Name||retinal degeneration 1|
|Allele Synonym(s)||Pdebrd1; rd; rd1; rd-1; rodless retina|
|Gene Symbol and Name||Pde6b, phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide|
|Strain of Origin||various|
|General Note||The following inbred strains are known to be homozygous for Pde6b |
|Molecular Note||Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C-to-A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain, has been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.|
|Allele Name||flexed tail|
|Gene Symbol and Name||f, flexed-tail|
|Strain of Origin||Not Specified|
|General Note|| |
The flexed-tail mutation appeared in a stock maintained by Dr. H.R. Hunt at Michigan State College (J:12951). Homozygotes are small at birth and have a transitory hypochromic, microcytic anemia characterized by a large number of siderocytes containing non-heme iron granules. Most homozygotes also have flexed tail and a belly spot, but these are not constant manifestations of the mutant. Because of the anemia there is probably greater postnatal mortality among f/f than among normal mice (J:14979).
The anemia begins on the 12th day of embryonic life when the liver first starts to produce blood cells (J:14979). It is most intense at 15 days of gestation and still severe at birth, but by 2 weeks of age has disappeared. Although adults have normal blood values, their response to hemopoietic stress is defective (J:5439, J:27511).
The results of numerous studies have led to the conclusion that the prenatal deficiency in number of erythrocytes and the defective response of adult erythropoietic cells are due to a delay in maturation of already committed erythroid stem cells, and that earlier uncommitted precursors are unaffected by f (J:5439, J:5654, J:5582).
An additional effect of f in homozygotes is defective heme synthesis, which occurs in fetal reticulocytes but not in adult reticulocytes nor in erythroblasts at earlier stages of maturation. In fetal reticulocytes there is normal uptake of iron but poor incorporation into hemoglobin (J:5439), probably as a result of reduced activity of delta-aminolevulinate synthetase and dehydratase (J:5591).
Fetal erythrocytes of f/f mice have more alpha than beta globin chains. In both f/f and wild-type fetal erythrocytes there is more alpha- than beta-chain mRNA; probably some regulatory mechanism bringing about equal alpha- and beta-chain synthesis exists in wild-type mice but is defective in f/f (J:5827, J:30711).
The tail abnormalities are first noticeable on the 14th day of gestation as abnormal differentiation of the intervertebral discs (J:13090). The possibility that abnormal heme synthesis could cause the tail and pigment defects in f/f mice has been discussed (J:5591).
It was suggested that flexed-tail might be a mutation in the mouse homolog Fancc of the gene defective in human Fanconi anemia, complementation group C, but no mutation in the Fancc gene or abnormalities in Fancc mRNA have been detected in f/f mutants (J:13598). Also, flexed-tail mice are not susceptible to increases in chromosomal aberrations induced by mitomycin C, a characteristic of Fancc mutant mice (J:35839).
This allele arose on a genetically undefined stock in 1927 and was subsequently transferred onto several genetic backgrounds to create the congenic and recombinant inbred lines Je/Le-f/f, FL1/ReJ, WB/ReJ-f/f and C57BL/6J-f/f. The phenotypes listed above might be associated with any of these strains; in most cases it was not specified.
|Molecular Note||Note that two conflicting reports (J:68377 and J:98445/J:128616) state that the underlying genetic defect in the flexed tail mouse is either in the Sfxn1 or the Smad5 gene.|
|Mutations Made By|| |
Mark Fleming, Children's Hospital Boston