All Phenotypes Tsn<Gt(OST63223)Lex> MGI Mouse

• at birth, homozygotes are smaller than wild-type mice

• homozygotes exhibit a 10%-30% reduction in birth weights relative to heterozygous or wild-type littermates

• at 5-6 months of age, homozygotes exhibit a significantly decreased lean body mass relative to heterozygous and wild-type mice (21.56 1.55 g versus 28.13 0.90 g and 25.28 1.25 g, respectively)

decreased body weight ( J:85466 )

• in addition to reduced birth weights, homozygotes display a significantly reduced body weight at 1 month of age

• major organ weights are proportionately reduced, despite the presence of normal cell volumes in various tissues

slow postnatal weight gain ( J:85466 )

• homozygotes display a reduced growth rate relative to wild-type littermates from birth to 96 days of age

• however, no significant weight differences are observed by 6 months of age

decreased body length ( J:85466 )

• at 5-6 months of age, homozygotes display reduced body lengths relative to heterozygous and wild-type littermates (9.1, 9.5, and 9.7 cm, respectively)

• however, bone densities remain unaffected

increased male germ cell apoptosis ( J:85466 )

• at 2 months of age, male homozygotes display a significant increase in the number of TUNEL-positive cells from primarily pachytene spermatocytes to metaphase I

• male germ apoptosis appears to precede seminiferous tubule vacuolization

abnormal testis morphology ( J:85466 )

• at 6-8 months of age, occasional male homozygotes display abnormal testicular morphology

seminiferous tubule degeneration ( J:85466 )

• starting at ~2 months of age, male homozygotes display progressive seminiferous tubule degeneration, not observed in wild-type males

• by 8 months of age, mutant tubules are heavily vacuolated

abnormal spermatogenesis ( J:85466 )

• spermatogenesis is severely disrupted; however, male fertility is preserved

oligozoospermia ( J:85466 )

• male homozygotes show an age-dependent reduction in sperm counts, first evident at 43 days of age

• by 9 months of age, male homozygotes show a ~67% reduction in sperm counts relative to male heterozygotes

• however, no significant differences are observed in FSH and LH levels, epididymal and seminal vesicle weights, or in sperm motility relative to heterozygous and wild-type mice

arrest of male meiosis ( J:85466 )

• male meiosis is arrested with a high level of cell death in meiotic prophase and at metaphase I

reduced female fertility ( J:85466 )

• when mated with heterozygous or wild-type males, female homozygotes average 68.8 2.2 days between litters, while control matings average 32.2 2.2 days between litters

• however, preliminary examination revealed no obvious defects in the female reproductive tract

decreased litter size ( J:85466 )

• female homozygotes produce smaller litters than female heterozygotes (4 versus 8 pups/litter, respectively)

increased abdominal fat pad weight ( J:85466 )

• at 5-6 months of age, homozygotes display a disproportionate accumulation of fat mass in the abdominal region, including the visceral, retroperitoneal, and surrounding subcutaneous fat pads

increased percent body fat/body weight ( J:85466 , J:185494 )

• at 5-6 months of age, homozygotes exhibit an increased % of total fat mass relative to heterozygous and wild-type mice (32.38% 2.37% vs 18.17% 2.01% and 6.55% 0.46%, respectively) (J:85466)

decreased aggression ( J:85466 )

• homozygotes appear more docile than control littermates

impaired coordination ( J:85466 )

• homozygotes of both sexes consistently fall from an accelerating rotarod sooner than wild-type controls

• however, the performance of both mutant and wild-type mice improves significantly over time, with no significant differences in the rates of improvement

• also, cerebellar anatomy and gross brain morphology remain relatively normal (not shown), despite major alterations of gene expression in the brain