Mice homozygous for the little spontaneous mutation are characterized by a deficiency in pituitary growth hormone (GH) along with prolactin and growth retardation. Because GH in the circulation regulates IGF-1, little homozygotes have approximately one-tenth the normal level of IGF-1. On the C57BL/6J background male homozygotes have been shown to have reduced fertility and female homozygotes show a delay in lactation. This mutation was transferred to the C3H/HeJ background for better assessment of the impact on bone mineral density (BMD). C3H/HeJ have high bone mineral density compared with C57BL/6J and this congenic shows a significant difference in the femoral BMD of little homozygotes, which have 0.61 mg/mm3, and heterozygotes, which have 0.691 mg/mm3, and a much higher BMD than homozygotes on the C57BL/6J background, which have 0.453 mg/mm3, or even heterozygotes on the C57BL/6J background, which have 0.482 mg/mm3. Assessment of whole body bone mineral density also shows that the increased bone mineral density of C3H/HeJ relative to C57BL/6J carries into the little homozygotes on each background. The reduction in body weight, IGF-1 levels, and comparative bone geometry are similar even though the bone mineral density is much higher on the C3H/HeJ background than the C57BL/6J background.
This congenic was made by transferring the Ghrhrlit mutation from the C57BL/6J-Ghrhrlit/J coisogenic strain onto the C3H/HeJ host strain by repeated backcross-intercross breeding, which began by breeding a homozygous female to a C3H/HeJ male. When this congenic reached backcross generation N10 it was then maintained by sibling intercrossing and at generation N10F16 embryos were generated for cryopreservation from homozygous males and C3H/HeJ females.
|Allele Synonym(s)||lit; litm|
|Gene Symbol and Name||Ghrhr, growth hormone releasing hormone receptor|
|Strain of Origin||C57BL/6J|
|Molecular Note||The mutation in little mice is a A-to-G transition in codon 60 that alters this residue from a aspartate to a glycine in the encoded protein (p.D60G). Reduced levels of mRNA were noted in total RNA derived from pituitary of homozygous mice, and in vitro assays demonstrated that no functional protein is made from this allele.|