These mice carry a spontaneous mutation at the Pou1f1 locus characterized by severe dwarfing, sterility, and hypothyroidism. The strain also carries the coat color mutation, leaden, as an aid for identifying genotypes.Read More +
Mice homozygous mice for the dwarf spontaneous mutation (Pou1f1dw) are characterized by severe dwarfing, sterility, and hypothyroidism. Adult dwarf mice are about one-fourth to one-third the size of wildtype mice. There is a lack of growth hormone, prolactin and thyroid stimulating hormone producing cells in the anterior pituitary leading to severe endocrine deficiency of these hormones. Homozygous mutant mice show a transient loss in cortical thymocytes associated with the primary defect in anterior pituitary.
The mutation dwarf (Pou1f1dw) arose in a stock of black silver mice obtained from an English fancier (William Turton of Ilkeson) in 1920. Dr. G. D. Snell found dwarf among the mouse stocks he had when at the Bussey Institute at Harvard University in 1921. He later received it at The Jackson Laboratory from Dr. MacDowell in 1948 after the 1947 Bar Harbor fire. A female carrier of dwarf that was brown (Tyrp1b) and chinchilla (Tyrc-ch) was mated to a jerker (Espnje) male that was also ruby (Hps5ru). A male offspring of this cross, carrying dwarf, ruby, jerker, brown and chinchilla, was mated to an ABY.B10 female. The ABY.B10 was a hybrid that was H2b. A.BY is congenic from a non-inbred, BY, which carried brachyury (T), bred onto A/Lilly and AWySn then this congenic was crossed to C57BL/10 to make the H2b strain hybrid for vigor. Mouse BY was A/a at the agouti locus. After crossing the male carrying dwarf, ruby, jerker, brown and chinchilla to the ABY.B10 female, the stock was then non-sibling mated for several generations and outcrossed once to piebald (Ednrbs) females that were segregating for other loci including leaden (Mlphln) and albino (Tyrc). In 1954 inbreeding and selection was started and at F13 in 1960 the stock was primarily agouti (A), leaden (Mlphln) and segregating dwarf (Pou1f1dw). In 1966 the stock was at F35 and called DW/J and was sent to The Jackson Laboratory Animal Resources Mutant Stocks Department. A line of compatible mice of the wild type genotype was then constructed to provide hosts for ovarian transplantation. This line used for transplantation was DW.C3-Mlph+ Pou1f1+/J (Stock No. 000681). DW/J was maintained by ovarian transplantation for many generations. DW/J was cryopreserved in 1997 at generation F104 by mating heterozygous females to homozygous males that had a pituitary transplant from heterozygous littermates and a T4 pellet implanted subcutaneously allowing them to breed.
|Allele Synonym(s)||dw; dwarf; Pit1dw; Pit1dwSn; Snell-Bagg pituitary dwarf; Snell's dwarf|
|Gene Symbol and Name||Pou1f1, POU domain, class 1, transcription factor 1|
|Strain of Origin||STOCK Pmelsi|
|General Note||Phenotypic Similarity to Human Syndrome: Secondary Hypothyroidism J:144823 |
This mutation arose in a stock of silver mice obtained from an English fancier (J:13120). Homozygous mutant mice are about one-fourth to one-third normal size and are sterile. The small size is due to a defective anterior pituitary in which there is a great deficiency of GH-producing, PRL-producing, and TSH-producing cells (J:6754, J:7211, J:12161). The anterior pituitary of the Pit1dw homozygote is already abnormal at birth with no identifiable GH or PRL cells (J:6684). GH and PRL synthesis is not detectable at any stages from birth to 6 weeks of age (J:6589), and there is probably also a deficiency of TSH and corticotropin (J:19241). Adult dwarf mouse pituitaries retain an embryonic, incompletely differentiated form of corticotrophs (J:13323). The defects in growth and fertility may be corrected by pituitary implants (J:13139) or by administration of pituitary hormones (J:30695, J:5085).
Two populations of cells give rise to thyrotrophs in the anterior pituitary in developing mouse embryos. The first population arises at day 12 in the rostral tip of the gland. This population is independent of Pit1, as it appears in Pit1dw mice, but it disappears by birth. The second population, which arises in the caudomedial portion of the gland at embryonic day 15.5, is Pit1-dependent, and is absent in Snell dwarf mice(J:17223).
Pit1dw mice have been reported to have a defective immune response that primarily affects the T cell system (J:19990), but other authors (J:6241, J:5638) have been unable to confirm these findings and attribute the previous results to secondary effects of dwarfing on overall vigor and nutritional status. Cross (J:2020) has shown that Pit1dw homozygous mice do develop normal immunocompetence, but that this development is delayed relative to that in normal littermates. Dwarf homozygotes have a severe deficiency of dopamine in the median eminence (J:6652).
|Molecular Note||A G-to-T transversion mutation in codon 261 converts a tryptophan residue in the homeodomain to a cysteine in the encoded protein (p.W261C).|
|Gene Symbol and Name||Mlph, melanophilin|
|Strain of Origin||C57BR|
|Molecular Note||This allele has a C-to-T transition at mRNA nucleotide position 266. This introduces a stop codon at arginine codon 31 (p.R31*) in the sequence of the normally spliced transcript and it also creates a new G-GT splice donor site in exon 2. Use of this alternative splice site yields a transcript with an in-frame 21 base pair deletion that deletes 7 amino acids from the translated protein. Northern blots failed to detect this size difference and did not find any change from normal in transcript expression level. Sequence analysis failed to detect any wild-type transcripts.|
Homozygotes require powdered food and easy access to water to survive. Homozygotes are often not weaned until 4 weeks of age.
When using the dwarf mouse strain in a publication, please cite the originating article(s) and include JAX stock #000643 in your Materials and Methods section.