B6.DW-Pou1f1^dw/J

Stock number: 000772
Product name: dwarf
Research areas: Cell Biology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Reproductive Biology Research

Description

These mice carry a spontaneous mutation at the Pou1f1 locus characterized by severe proportional dwarfing, sterility, and hypothyroidism.

Detailed description

Mice homozygous mice for the dwarf spontaneous mutation (Pou1f1^dw) are characterized by severe proportional 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.

Development

A heterozygous dwarf (Pou1f1^dw/+) male from strain DW/J at generation F45 was crossed to a C57BL/6J female in 1969 to start the B6.DW line. Each generation thereafter a tested male carrier was backcrossed to a C57BL/6J female to N11. At N11 the strain was maintained by mating tested heterozygous siblings to F9. The strain was cryopreserved in 1981 by mating N11F9 tested heterozygous dwarf males to C57BL/6J females.

Allele

Symbol: Pou1f1^dw
Name: dwarf
MGI accession ID: MGI:1856024
Generation method: Spontaneous
Marker symbol: Pou1f1
Marker name: POU domain, class 1, transcription factor 1
Chromosome: 16
Strain of origin: STOCK Pmel^si
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).
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 Pit1^dw 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 Pit1^dw 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).

Pit1^dw 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 Pit1^dw 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).