Phenotypes associated with this allele

• Allele Symbol: Six6^tm1Rsd
• Allele Name: targeted mutation 1, Michael G Rosenfeld
• Allele ID: MGI:3613016
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Six6^tm1Rsd/Six6^tm1Rsd	either: 129 or (involves: 129S1/Sv * 129X1/SvJ)	MGI:3613489
hm2	Six6^tm1Rsd/Six6^tm1Rsd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6452970

Genotype
MGI:3613489

hm1

• Allelic Composition: Six6^tm1Rsd/Six6^tm1Rsd
• Genetic Background: either: 129 or (involves: 129S1/Sv * 129X1/SvJ)

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

vision/eye

absent optic nerve ( J:104339 )

• Background Sensitivity: more common on a mixed background and less common on a pure 129/Sv background

• occurs often and affecting the optic chiasm as well

abnormal retina morphology ( J:104339 )

• phenotypes are more severe on a "mixed" background and less severe when the background consists only of 129/Sv

abnormal retina ganglion layer morphology ( J:104339 )

• less cell proliferation

• 20% decrease in ganglion cell layer by 35 days of age

retina hypoplasia ( J:104339 )

• variable

nervous system

pituitary gland hypoplasia ( J:104339 )

• Background Sensitivity: more common on a "mixed" background and less severe on a 129/Sv background

absent optic nerve ( J:104339 )

• Background Sensitivity: more common on a mixed background and less common on a pure 129/Sv background

• occurs often and affecting the optic chiasm as well

endocrine/exocrine glands

pituitary gland hypoplasia ( J:104339 )

• Background Sensitivity: more common on a "mixed" background and less severe on a 129/Sv background

Genotype
MGI:6452970

hm2

• Allelic Composition: Six6^tm1Rsd/Six6^tm1Rsd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

reproductive system

reproductive system phenotype ( J:168233 )

♂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

decreased seminal vesicle weight ( J:168233 )

♂ • average seminal vesicle weight is significantly reduced at 4-6 months of age

abnormal ovary morphology ( J:168233 )

♀ • 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

decreased corpora lutea number ( J:168233 )

♀ • number of corpora lutea per ovary is severely reduced at 4-6 months of age

ovarian follicular cyst ( J:168233 )

♀ • large cystic follicles are commonly observed

small ovary ( J:168233 )

♀ • at 4-6 months of age, diestrus ovaries are significantly smaller than those in wild-type or heterozygous females

decreased ovary weight ( J:168233 )

♀ • average ovary weight is significantly reduced at 4-6 months of age

anovulation ( J:168233 )

♀ • females fail to show any evidence of successful ovulation

prolonged estrus ( J:168233 )

♀ • % of time spent in estrus is significantly increased

short metestrus ( J:168233 )

♀ • % of time spent in metestrus is significantly decreased

short proestrus ( J:168233 )

♀ • % of time spent in proestrus is significantly decreased

prolonged estrous cycle ( J:168233 )

♀ • average estrous cycle length is doubled, resulting in significantly more time spent in estrus

reduced female fertility ( J:168233 )

♀ • 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

reduced male fertility ( J:168233 )

♂ • 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

homeostasis/metabolism phenotype ( J:168233 , J:168233 )

♀N • at 4-6 months of age, female serum 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 (J:168233)

♀N • immunohistochemical analysis showed normal numbers of luteinizing hormone beta-expressing gonadotrope cells within the anterior pituitary, suggesting normal gonadotrope function (J:168233)

♂N • at 4-6 months of age, a non-significant (~35%) decrease is noted in male serum luteinizing hormone (LH) and testosterone levels relative to wild-type or heterozygous males (J:168233)

♂N • however, males are able to generate a normal LH surge in response to gonadotropin-releasing hormone (GnRH) (J:168233)

decreased circulating follicle stimulating hormone level ( J:168233 )

♂ • at 4-6 months of age, male serum FSH levels show a ~75% reduction relative to those in wild-type or heterozygous males

abnormal protein level ( J:168233 )

• adult mice show a dramatic decrease in both GnRH mRNA and protein expression levels

nervous system

abnormal neuroendocrine cell morphology ( J:168233 )

• 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

abnormal axon morphology ( J:168233 )

• immunostaining of the median eminence showed a marked reduction in GnRH neuron axon density

decreased neuron number ( J:168233 , J:168233 )

• 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 (J:168233)

• total numbers of GnRH neurons are also significantly decreased at P1 but not at E13.5 (J:168233)

♀ • 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 (J:168233)

growth/size/body

ovarian follicular cyst ( J:168233 )

♀ • large cystic follicles are commonly observed

endocrine/exocrine glands

abnormal neuroendocrine cell morphology ( J:168233 )

• 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

decreased seminal vesicle weight ( J:168233 )

♂ • average seminal vesicle weight is significantly reduced at 4-6 months of age

abnormal ovary morphology ( J:168233 )

♀ • 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

decreased corpora lutea number ( J:168233 )

♀ • number of corpora lutea per ovary is severely reduced at 4-6 months of age

ovarian follicular cyst ( J:168233 )

♀ • large cystic follicles are commonly observed

small ovary ( J:168233 )

♀ • at 4-6 months of age, diestrus ovaries are significantly smaller than those in wild-type or heterozygous females

decreased ovary weight ( J:168233 )

♀ • average ovary weight is significantly reduced at 4-6 months of age

behavior/neurological

decreased copulatory plug deposition ( J:168233 )

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