Phenotypes associated with this allele

• Allele Symbol: Cyp19a1^tm1Sih
• Allele Name: targeted mutation 1, Shin-ichiro Honda
• Allele ID: MGI:2389548
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cyp19a1^tm1Sih/Cyp19a1^tm1Sih	involves: 129S/SvEv	MGI:2658880
hm2	Cyp19a1^tm1Sih/Cyp19a1^tm1Sih	involves: 129S/SvEv * C57BL/6	MGI:4367348

Genotype
MGI:2658880

hm1

• Allelic Composition: Cyp19a1^tm1Sih/Cyp19a1^tm1Sih
• Genetic Background: involves: 129S/SvEv

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

behavior/neurological

decreased mounting behavior ( J:51076 )

♂ • at 10-18 weeks of age, male homozygotes exhibit significantly prolonged latencies to first mount and reduced mount frequency in response to receptive stimulus females during a 30-min sexual behavior test

♂ • 5 of 12 male homozygotes never mounted during the observation period

♂ • however, all mutant males sniffed and licked the genital area of stimulus females, indicating potential sexual motivation

sexually aggressive behavior ( J:51076 )

• 2 of 12 male homozygotes showed significant aggressive behavior (chasing and biting) towards estrous females during male copulatory tests, not observed in wild-type males

reproductive system

abnormal ovary morphology ( J:51076 )

♀

absent corpus luteum ( J:51076 )

♀ • at 10-12 weeks of age, mutant ovaries lack corpora lutea

abnormal uterus development ( J:51076 )

♀ • at 10-12 weeks of age, mutant uteri appear significantly underdeveloped relative to wild-type

decreased uterus weight ( J:51076 )

♀ • at 10-12 weeks of age, mutant uteri weigh less than 30% of wild-type uteri

female infertility ( J:51076 )

♀ • female homozygotes are infertile due to a disrupted ovarian cycle

reduced male fertility ( J:51076 )

♂ • at 14-17 weeks of age, only 1 of 10 male homozygotes gave a high mount frequency (17 times/30 min) and sired litters

♂ • however, no differences were noted between mutant and wild-type testes weights at 12-16 weeks of age, and mutant males had active sperm in testes and epididymides

endocrine/exocrine glands

abnormal salivary gland morphology ( J:216958 )

♀ • more salivary gland cells exhibit a fatty change than in controls

salivary gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice

♀ • many CD4+ T cells and B220+ cells infiltrate the salivary glands

abnormal ovary morphology ( J:51076 )

♀

absent corpus luteum ( J:51076 )

♀ • at 10-12 weeks of age, mutant ovaries lack corpora lutea

lacrimal gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice

adipose tissue

increased abdominal adipose tissue amount ( J:216958 )

♀ • volume of abdominal white adipose tissue in females at 12 months of age is greater than in wild-type mice

♀ • weight of white adipose tissue is increased

increased total body fat amount ( J:51076 )

• at 10-12 weeks of age, homozygotes show significantly increased internal fat relative to wild-type controls

abnormal white adipose tissue morphology ( J:216958 )

♀ • proportion of dendritic cells and macrophages in the white adipose tissue is higher than in wild-type mice

♀ • accumulated macrophages in adipose tissue forms a crown-like structure

♀ • mice show an increase in number of F4/80+ macrophages in the cervical white adipose tissue around the salivary glands

♀ • accumulation of mononuclear cells around adipocytes

♀ • marker analysis suggests enhanced migration and maturation of activated M1 macrophages in the white adipose tissue

digestive/alimentary system

abnormal salivary gland morphology ( J:216958 )

♀ • more salivary gland cells exhibit a fatty change than in controls

salivary gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice

♀ • many CD4+ T cells and B220+ cells infiltrate the salivary glands

hematopoietic system

increased dendritic cell number ( J:216958 )

♀ • absolute numbers of dendritic cells in 12 month old mutants is higher

♀ • proportion of dendritic cells in the white adipose tissue is higher than in wild-type mice

increased macrophage cell number ( J:216958 )

♀ • absolute numbers of macrophages in 12 month old mutants is higher

♀ • proportion of macrophages in the white adipose tissue is higher than in wild-type mice

immune system

salivary gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice

♀ • many CD4+ T cells and B220+ cells infiltrate the salivary glands

lacrimal gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice

increased dendritic cell number ( J:216958 )

♀ • absolute numbers of dendritic cells in 12 month old mutants is higher

♀ • proportion of dendritic cells in the white adipose tissue is higher than in wild-type mice

increased macrophage cell number ( J:216958 )

♀ • absolute numbers of macrophages in 12 month old mutants is higher

♀ • proportion of macrophages in the white adipose tissue is higher than in wild-type mice

increased susceptibility to autoimmune disorder ( J:216958 )

♀ • mice show the development on inflammatory lesions in the lacrimal and salivary glands after 12 months of age, resembling those of human Sjogren Syndrome

increased autoantibody level ( J:216958 )

♀ • mice exhibit higher levels of serum autoantibodies, such as anti-SSA, anti-SSB, and anti-ssDNA

increased anti-single stranded DNA antibody level ( J:216958 )

♀

vision/eye

lacrimal gland inflammation ( J:216958 )

♀ • severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Sjogren's syndrome		DOID:12894	OMIM:270150	J:216958

Genotype
MGI:4367348

hm2

• Allelic Composition: Cyp19a1^tm1Sih/Cyp19a1^tm1Sih
• Genetic Background: involves: 129S/SvEv * C57BL/6

behavior/neurological

decreased aggression towards male mice ( J:84396 )

♂ • resident male homozygotes display a significantly lower incidence of aggressive behavior toward group-housed olfactory-bulbectomized (OBX) male intruders in a 15-min resident-intruder paradigm test

♂ • the number of bouts, duration and latency to the second act of aggressive behavior are significantly attenuated relative to those in wild-type controls

abnormal paternal behavior ( J:84396 )

♂ • 73% of male homozygotes exhibit infanticidal behavior toward pups

♂ • male homozygotes exhibit a reduced incidence of pup retrieving and nursing behaviors relative to wild-type males

♂ • however, no differences in the incidence of crouching behavior are observed

abnormal sexual interaction ( J:84396 )

♂ • male homozygotes display defects in male sexual behavior including intromission and mounting behavior

abnormal copulation behavior ( J:84396 )

♂ • male homozygotes display defects in the motivational and consummatory aspects of male copulatory behavior

abnormal intromission ( J:84396 )

♂ • only 10% of male homozygotes show intromission activities during a 30-min test

♂ • male homozygotes display significant reductions in intromission frequencies relative to wild-type controls

decreased mounting behavior ( J:84396 )

♂ • only 24% of male homozygotes show mount activities during a 30-min test

♂ • male homozygotes display significant reductions in mount frequencies relative to wild-type controls

sexually aggressive behavior ( J:84396 )

♂ • male homozygotes display a significantly high incidence of aggressive behavior toward estrous females during male copulatory tests; not observed in wild-type males

♂ • both the number of bouts and duration of the first and second act of aggressive behavior are increased relative to those in wild-type controls

reproductive system

male infertility ( J:84396 )

♂ • at 8-12 weeks of age, 73% of male homozygotes are infertile

reduced male fertility ( J:84396 )

♂ • gonadally intact male homozygotes display a lower fertility rate than wild-type males in a long-term fertility test (23% vs 90%, respectively)

failure of ejaculation ( J:84396 )

♂ • no male homozygotes exhibit ejaculation during a 30-min test

♂ • however, noncontact penile erection is not significantly altered