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Phenotypes Associated with This Genotype
Genotype
MGI:6452970
Allelic
Composition
Six6tm1Rsd/Six6tm1Rsd
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Six6tm1Rsd mutation (0 available); any Six6 mutation (16 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• at 4-6 months of age, no significant differences are observed in relative testis weight, average sperm count, testis architecture or spermatogenesis relative to wild-type or heterozygous males
• average seminal vesicle weight is significantly reduced at 4-6 months of age
• at 4-6 months of age, extensive areas of cells with enlarged cytoplasm are observed in the stroma, indicating a failure to transform granulosa cells into luteal tissue
• number of corpora lutea per ovary is severely reduced at 4-6 months of age
• large cystic follicles are commonly observed
• at 4-6 months of age, diestrus ovaries are significantly smaller than those in wild-type or heterozygous females
• average ovary weight is significantly reduced at 4-6 months of age
• females fail to show any evidence of successful ovulation
• % of time spent in estrus is significantly increased
• % of time spent in metestrus is significantly decreased
• % of time spent in proestrus is significantly decreased
• average estrous cycle length is doubled, resulting in significantly more time spent in estrus
• when housed singly with an age-matched C57BL/6J male mouse, only 12.5% of 8-wk-old homozygous females assessed produce a single litter of 5 pups, indicating a striking reduction in female fertility
• however, timing of vaginal opening is normal, suggesting that onset of puberty is not delayed
• when housed singly with an age-matched C57BL/6J female mouse, 8-wk-old homozygous males produce a significantly lower number of litters during a 3-month period than wild-type or heterozygous males
• however, the number of pups per litter is not significantly altered

homeostasis/metabolism
N
• at 4-6 months of age, female serum luteinizing hormone (LH) levels are nearly doubled, consistent with the presence of cystic follicles; however, neither LH nor FSH basal serum levels are significantly altered relative to those in wild-type or heterozygous females and immunohistochemical analysis showed normal numbers of luteinizing hormone beta-expressing gonadotrope cells within the anterior pituitary, suggesting normal gonadotrope function
• at 4-6 months of age, a non-significant (~35%) decrease is noted in male serum LH and testosterone levels relative to wild-type or heterozygous males; however, males are able to generate a normal LH surge in response to gonadotropin-releasing hormone (GnRH)
• at 4-6 months of age, male serum FSH levels show a ~75% reduction relative to those in wild-type or heterozygous males
• adult mice show a dramatic decrease in both GnRH mRNA and protein expression levels

nervous system
• immunostaining of the median eminence showed a marked reduction in GnRH neuron axon density
• analysis of gonadotropin-releasing hormone (GnRH) expression in the hypothalamus revealed an 89% decrease in total GnRH neuron numbers in females at 4 months of age, with a similar 84% decrease in males at 4-5 months of age
• total numbers of GnRH neurons are also significantly decreased at P1 but not at E13.5
• immunostaining of the median eminence showed a marked reduction in GnRH neuron axon density
• females show reduced numbers of tyrosine hydroxylase (TH)-positive neurons within the anteroventral periventricular (AVPV) region as well as decreased targeting to the median eminence

growth/size/body
• large cystic follicles are commonly observed

endocrine/exocrine glands
• immunostaining of the median eminence showed a marked reduction in GnRH neuron axon density
• analysis of gonadotropin-releasing hormone (GnRH) expression in the hypothalamus revealed an 89% decrease in total GnRH neuron numbers in females at 4 months of age, with a similar 84% decrease in males at 4-5 months of age
• total numbers of GnRH neurons are also significantly decreased at P1 but not at E13.5
• average seminal vesicle weight is significantly reduced at 4-6 months of age
• at 4-6 months of age, extensive areas of cells with enlarged cytoplasm are observed in the stroma, indicating a failure to transform granulosa cells into luteal tissue
• number of corpora lutea per ovary is severely reduced at 4-6 months of age
• large cystic follicles are commonly observed
• at 4-6 months of age, diestrus ovaries are significantly smaller than those in wild-type or heterozygous females
• average ovary weight is significantly reduced at 4-6 months of age

behavior/neurological
• only 33% of females housed with a homozygous male form a visible plug after 10 days of cohabitation


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
01/28/2026
MGI 6.24
The Jackson Laboratory