Phenotypes Associated with This Genotype

Genotype
MGI:3582621

• Allelic Composition: Rbl1^tm1Tyj/Rbl1^tm1Tyj; Rbl2^tm1Tyj/Rbl2^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

neonatal lethality, complete penetrance ( J:34725 )

• generally, double mutants are born alive but die shortly after birth

perinatal lethality, incomplete penetrance ( J:34725 )

• occasionally, double mutant mice are not removed from their amniotic sacs by their mothers and either are born dead or die partly as a result of maternal rejection

skeleton

abnormal craniofacial bone morphology ( J:34725 )

interparietal bone hypoplasia ( J:34725 )

• at 19.0 dpc, the interparietal bone of double mutant mice appears underdeveloped; most other cranial bones develop normally

abnormal supraoccipital bone morphology ( J:34725 )

• at 19.0 dpc, the supraoccipital bone of double mutant mice appears slightly underdeveloped

absent incisors ( J:82802 )

• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue

small incisors ( J:82802 )

• most double mutant embryos exhibit incisors microdontia

abnormal tooth development ( J:82802 )

• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer

abnormal limb bone morphology ( J:34725 )

abnormal humerus morphology ( J:34725 )

• at 16.0 dpc, the mutant humerus shows complete lack of ossification

increased diameter of humerus ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the humerus

short humerus ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the humerus

short radius ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the radius

increased diameter of radius ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the radius

short ulna ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the ulna

increased diameter of ulna ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the ulna

abnormal tracheal cartilage morphology ( J:34725 )

• at 18.0 dpc, some double mutants display abnormal tracheal cartilage formation, contributing to airway dysfunction and possibly neonatal lethality

abnormal long bone epiphyseal plate morphology ( J:34725 )

• at 18 dpc, the growth plates of mutant humerus appear widened, the epiphyses are deformed and thickened, and the zone of flattened cells elongated

abnormal long bone epiphyseal plate proliferative zone ( J:34725 )

• chondrocytes in the epiphyseal centers of mutant humeri proliferate at an increased rate and reach and higher density

• chondrocytes in the zone of flattened cells exhibit a delay in the cell cycle withdrawal and hypertrophy associated with terminal differentiation

• however, chondrocytes eventually stop proliferating in mutant growth plates

increased width of hypertrophic chondrocyte zone ( J:34725 )

• in 18.0 dpc mutant humerus, hypertrophic chondrocytes fail to form well-organized columns, and ossification of cancellous bone begins at an increased distance from the articular surface

abnormal rib development ( J:34725 )

• abnormal rib development may prevent adequate lung expansion and inflation, contributing to neonatal lethality

small thoracic cage ( J:34725 )

• at 16.0 dpc, double mutants show a reduced rib cage size

abnormal chondrocyte morphology ( J:34725 )

• at 18.0 dpc, chondrocyte density in the epiphyseal centers of mutant humeri is increased by ~2-fold; at 16.5 dpc, chondrocyte density is increased by ~30%

delayed endochondral bone ossification ( J:34725 )

• at 16.0 dpc, double mutants display reduced ossification of the long bones of the fore- and hindlimbs, including complete loss of ossification in the humerus

craniofacial

abnormal craniofacial bone morphology ( J:34725 )

interparietal bone hypoplasia ( J:34725 )

• at 19.0 dpc, the interparietal bone of double mutant mice appears underdeveloped; most other cranial bones develop normally

abnormal supraoccipital bone morphology ( J:34725 )

• at 19.0 dpc, the supraoccipital bone of double mutant mice appears slightly underdeveloped

absent incisors ( J:82802 )

• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue

small incisors ( J:82802 )

• most double mutant embryos exhibit incisors microdontia

abnormal tooth development ( J:82802 )

• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer

short snout ( J:34725 )

• beginning at 15.0-16.0 dpc, double mutants display a shortened snout

limbs/digits/tail

abnormal forelimb morphology ( J:34725 )

abnormal limb bone morphology ( J:34725 )

abnormal humerus morphology ( J:34725 )

• at 16.0 dpc, the mutant humerus shows complete lack of ossification

increased diameter of humerus ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the humerus

short humerus ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the humerus

short radius ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the radius

increased diameter of radius ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the radius

short ulna ( J:34725 )

• at 19.0 dpc, double mutants show abnormal shortening of the ulna

increased diameter of ulna ( J:34725 )

• at 19.0 dpc, double mutants show abnormal thickening of the ulna

short limbs ( J:34725 )

• beginning at 15.0-16.0 dpc, double mutants have significantly shorter limbs

respiratory system

abnormal tracheal cartilage morphology ( J:34725 )

• at 18.0 dpc, some double mutants display abnormal tracheal cartilage formation, contributing to airway dysfunction and possibly neonatal lethality

abnormal breathing pattern ( J:34725 )

• prior to death, double mutant neonates exhibit breathing abnormalities and poor oxygenation

apnea ( J:34725 )

• in double mutant neonates, abnormal endocranial bone formation may result in compression of the cervical spinal canal and observed lethal apnea

growth/size/body

absent incisors ( J:82802 )

• a few double mutant embryos display incisors anodontia with undifferentiated mesenchymal tissue

small incisors ( J:82802 )

• most double mutant embryos exhibit incisors microdontia

abnormal tooth development ( J:82802 )

• when present, the tooth germ of double mutant embryos shows variable degrees of microdontia along with hypoplasia and disorganization of the odontoblast layer

short snout ( J:34725 )

• beginning at 15.0-16.0 dpc, double mutants display a shortened snout

decreased body size ( J:34725 )

• at 18.5 dpc, double mutants are up to 30% smaller than littermates

decreased fetal size ( J:34725 )

• beginning at 15.0-16.0 dpc, double mutant embryos display a significant reduction in size

distended abdomen ( J:34725 )

• beginning at 15.0-16.0 dpc, double mutants display a moderately distended abdomen

endocrine/exocrine glands

enlarged sebaceous gland ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently display hyperplasic sebaceous glands

integument

abnormal keratinocyte differentiation ( J:82802 )

• newborn double homozygotes exhibit abnormal terminal differentiation of epidermal keratinocytes

• in addition, grafts of double mutant epidermis placed onto NOD Prkdc^scid mice show aberrant keratinocyte differentiation and hyperproliferation in the basal cells of interfollicular epidermis; proliferating cells are also detected in some cells of the suprabasal layer

enlarged sebaceous gland ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently display hyperplasic sebaceous glands

abnormal awl hair morphology ( J:82802 )

abnormal guard hair morphology ( J:82802 )

abnormal zigzag hair morphology ( J:82802 )

abnormal hair follicle development ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently exhibit multiple dysplastic hair follicles sharing a single hair channel as well as multiple follicular keratin-filled cysts

underdeveloped hair follicles ( J:82802 )

• newborn double homozygotes display a developmental delay in hair follicle formation that is associated with decreased Bmp4-dependent signaling in the epidermis

• this delay is first apparent at 14.5 dpc, concomitant with a severe reduction in the number of hair germs, and persists at 16.5 and 18.5 dpc, suggesting impaired morphogenesis and development of both tylotrich and nontylotrich hair follicles

• normal hair growth is restored when grafts of double mutant epidermis are placed onto NOD Prkdc^scid mice: at 4 weeks after transplantation, mutant skin grafts show normal anagen hair follicles with normal epithelial layers and hair bulbs

• in spite of normal hair formation, mutant skin grafts display several defects in hair morphogenesis, development and cycling

abnormal hair follicle orientation ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently have twisted hair follicles lying in parallel to the epidermal surface

decreased hair follicle number ( J:82802 )

• newborn double homozygotes show a generalized reduction in the number of hair follicles

• notably, at 4 weeks after transplantation, grafts of double mutant epidermis placed onto NOD Prkdc^scid mice display a 3-fold increase in the number of hair follicles

delayed emergence of vibrissae ( J:82802 )

• at 14.5 dpc, double mutant embryos exhibit a developmental delay of whiskers

abnormal hair cycle ( J:82802 )

• at 8 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice continue to display most hair follicles in anagen as opposed to the expected resting telogen phase

parakeratosis ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently display parakeratosis

abnormal epidermis stratum granulosum morphology ( J:82802 )

• newborn double homozygotes show a decrease in the number and size of keratohyalin granules of the stratum granulosum

epidermal hyperplasia ( J:82802 )

• at 4 weeks after transplantation, double mutant skin grafts placed onto NOD Prkdc^scid mice frequently display epidermal hyperplasia

cellular

abnormal keratinocyte differentiation ( J:82802 )

• newborn double homozygotes exhibit abnormal terminal differentiation of epidermal keratinocytes

• in addition, grafts of double mutant epidermis placed onto NOD Prkdc^scid mice show aberrant keratinocyte differentiation and hyperproliferation in the basal cells of interfollicular epidermis; proliferating cells are also detected in some cells of the suprabasal layer