Mice homozygous for the jerker spontaneous mutation (Espnje) show behavior typical of the circling mutants - head-tossing, circling, and hyperactivity. Homozygous mutant mice are deaf from birth and have no detectable stimulus-related cochlear potential at any stage. The abnormal behavior and deafness are associated with postnatal degeneration of the sensory cells of the cochlea and the sacculus and utriculus in homozygotes. The primary influence of the jerker gene appears to be on the apical hair cells, not development of neural structures. Heterozygous jerker mice undergo a similar type of degeneration, but the onset is delayed. Auditory brainstem response is totally absent in homozygotes while heterozygous mice undergo a progressive impairment with age.
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. JE/Le mice are also homozygous for the nonagouti (a) and ruby-eye (Hps6ru) mutations.
The jerker mutation, Espnje, was originally part of the mouse fancy, collected for it’s dancing phenotype. It was given by a mouse fancier to Dr. Hans Gruneberg prior to 1941. It was sent from Dr. R. A. Fisher to Dr. G. D. Snell at The Jackson Laboratory in 1948 in a strain containing the mutations flexed (f) and ruby (Hps6ru). It was bred by sibling and non-sibling matings holding flexed and ruby homozygous while jerker segregated in the stock. Two outcrosses were made to C57 in the 1950s. Starting in 1970 only sibling matings were used, again with flexed and ruby homozygous while jerker was kept segregating. In 1975 this strain reached inbreeding generation F20, in 1986 F50, and in 1989 F63. Embryos were generated for cryopreservation by breeding f/f Hps6ru/Hps6ru Espnje/+ females with f/f Hps6ru/Hps6ru Espnje/Espnje males.
|Gene Symbol and Name||Hps6, HPS6, biogenesis of lysosomal organelles complex 2 subunit 3|
|Strain of Origin||Danforth's Stock a Pmelsi Ednrbs|
|Molecular Note||Sequence analysis identified an in frame deletion of codons 187, 188, and 189 encoding histidine, cysteine, and proline, respectively.|
|Gene Symbol and Name||Espn, espin|
|Strain of Origin||fancier's dancing mouse|
|Molecular Note||A single nucleotide deletion (G) at position 2426 of the Espn gene results in a frameshift mutation and premature stop in the C-terminal actin binding domain. Normal levels of mRNA are observed, but no accumulation of protein is observed in the jerker mouse.|
|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
When using the jerker ruby-eye flexed tail mouse strain in a publication, please include JAX stock #000259 in your Materials and Methods section.