The Mecp2 knockout mutation is X-linked; therefore the Mecp2-deficient mice are Mecp2-/- (homozygous) females and Mecp2-/Y (hemizygous) males.
Mecp2 null mice are viable and appear normal at birth. No Mecp2 gene product (mRNA or protein) is detected in tissues. Mobility problems are apparent at 3-8 weeks of age. Mice exhibit hindlimb clasping and uneven breathing. An uneven wearing of teeth associated with misalignment of the jaws is observed in 50% of the animals. Adult males do not mate and their testes remain internal although sperm are present in the cauda epididymis. Symptom progression is variable, but mice can be expected to undergo weight loss, shivering, continued mobility problems before succumbing. Expected lifespan is approximately 50-60 days.
Heterozygous female mice display mobility problems and hindlimb clasping starting at about 6 months, but the symptoms are reported not to be progressive.
This Mecp2 knockout strain is useful for studying Rett Syndrome.
The Jackson Laboratory maintains this strain by breeding females heterozygous for the X-linked Mecp2 knockout mutation with C57BL/6J males. It has been our experience that less than 1% of all offspring genotype as "homozygous" females (120 of 36,437 females; July 2020). A cohort of "homozygous" females examined for karyotype were found to be XO. In general, the "homozygous" females present much the same as hemizygous males, with obesity, hind limb clasping, gradual decline in hind limb mobility and death between 50-100 days of age. In addition, rare instances of an obese heterozygous female has also been noted in the colony, which could possibly represent the same phenomenon. When identified in our colony, "homozygous" females are removed and the breeding unit that produced it is discontinued.
Importation of this model was supported in part by the Rett Syndrome Research Foundation.
